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Sample records for inducing intestinal lesions

  1. Radiation-induced intestinal lesions. Prognosis and surgical management

    International Nuclear Information System (INIS)

    Van Haecke, P.; Vitaux, J.; Michot, F.; Hay, J.-M.; Flamant, Y.; Maillard, J.-N.

    1981-01-01

    Thirteen patients with intestinal lesions consecutive to radiotherapy for carcinoma of the uterus were operated upon between 1973 and 1979. The small bowel was involved in 9 patients and the colon and rectum in 4 patients. Urinary tract lesions were associated in 3 patients of each group. Intestinal necrosis, progression of the lesions and extensive pelvic fibrosis were the only criteria of poor prognosis. Twenty-two operations were performed: 4 for urinary tract lesions and 18 for intestinal lesions. Five patients died during the immediate post-operative period and five died within 2 to 30 months after surgery, including 4 whose carcinoma recurred. The operative technique should be selected according to the extent and severity of radiation-induced damage, as determined by pre-operative examination and thorough exploration of the abdominal cavity once opened. Limited lesions of the small bowel can be treated by resection, but intestinal bypass with latero-lateral anastomosis seems to be preferable in cases with extensive lesions. Patients with colorectal lesions should have defunctioning colostomy prior to any other procedure dictated by the state of affairs. Multiple anastomosis, extensive resections and excessive dissections should be avoided [fr

  2. Oral and nasal administration of chicken type II collagen suppresses adjuvant arthritis in rats with intestinal lesions induced by meloxicam.

    Science.gov (United States)

    Zheng, Yong-Qiu; Wei, Wei; Shen, Yu-Xian; Dai, Min; Liu, Li-Hua

    2004-11-01

    To investigate the curative effects of oral and nasal administration of chicken type II collagen (CII) on adjuvant arthritis (AA) in rats with meloxicam-induced intestinal lesions. AA model in Sprague-Dawley (SD) rats with or without intestinal lesions induced by meloxicam was established and those rats were divided randomly into six groups which included AA model, AA model+meloxicam, AA model+oral CII, AA model+nasal CII, AA model+ meloxicam+oral C II and AA model+meloxicam+nasal CII (n = 12). Rats was treated with meloxicam intragastrically for 7 d from d 14 after immunization with complete Freund's adjuvant (CFA), and then treated with chicken CII intragastrically or nasally for 7 d. Histological changes of right hind knees were examined. Hind paw secondary swelling and intestinal lesions were evaluated. Synoviocyte proliferation was measured by 3-(4,5-dimethylthiazol-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide (MTT) method. Activities of myeloperoxidase (MPO) and diamine oxidase (DAO) from supernatants of intestinal homogenates were assayed by spectrophotometric analysis. Intragastrical administration of meloxicam (1.5 mg/kg) induced multiple intestinal lesions in AA rats. There was a significant decrease of intestinal DAO activities in AA+meloxicam group (P<0.01) and AA model group (P<0.01) compared with normal group. DAO activities of intestinal homogenates in AA+meloxicam group were significantly less than those in AA rats (P<0.01). There was a significant increase of intestinal MPO activities in AA+meloxicam group compared with normal control (P<0.01). Oral or nasal administration of CII (20 microg/kg) could suppress the secondary hind paw swelling(P<0.05 for oral CII; P<0.01 for nasal CII), synoviocyte proliferation (P<0.01) and histopathological degradation in AA rats, but they had no significant effects on DAO and MPO changes. However, oral administration of CII (20 microg/kg) showed the limited efficacy on arthritis in AA+meloxicam model and the

  3. Intestinal lesions induced by radiotherapy of malignant pelvic tumors. 2 cases

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    Manigand, G; Pointud, P; Foulon, D; Montely, J M; Testas, P; Paillas, J; Deparis, M [Hopital de Bicetre, 94 - le Kremlin-Bicetre (France)

    1976-11-16

    Intestinal lesions after radiotherapy for pelvic malignant tumors are of two types: ulcerative colitis with stenosis and hemorrhage sometimes severe and repeated, and ileal involvement with focal ischemic lesions and malabsorption responsible for nutritional disorders. It is difficult to distinguish them from a recurrence of the tumor in spite of endoscopy, arteriography and biopsy. The course in 3 stages is of great value in diagnosis. A reduction in the frequency of such complications may be hoped for by assessment and exclusion of predisposing factors, by strict observance of therapeutic rules. They are serious owing to the marked irreversible conjunctivo-vascular changes and the fragility of the irradiated tissues during operation.

  4. Modification of radiation induced intestinal lesions by Aegle marmelos fruit extract, an Indian medicinal plant

    International Nuclear Information System (INIS)

    Agrawal, Annapurna; Jahan, Swafiya; Goyal, R.K.

    2012-01-01

    Recently, some plant extracts have been screened out against radiation and found to be quite promising. Aegle marmelos (Bael), belonging to family Rutaceae, fruits are very good source of proteins which form 5.12% of the edible portion. It is claimed to be useful in treating pain, fever, inflammation, respiratory disorders, cardiac disorders, dysentery and diarrhea. The ripe fruit is used for the treatment of digestive and stomachic complications. Aegle marmelos is a useful medicine for herbalist and it holds a reputed position in Ayurvedic system of medicine. Protection of intestinal constituents by Aegle marmelos extract (AME) was studied after exposure to 6 Gy gamma radiations in mice. For this purpose, Swiss albino mice were divided in various groups. Group I was administered with double distilled water (DDW), volume equal to AME (100 mg/kg body wt./animal), by oral gavage to serve as normal. Group II was administered orally AME extract once daily at a dose of 100 mg/kg b.wt./animal for 5 consecutive days. Group III was exposed to 6 Gy gamma radiations to serve as irradiated control. Group IV was treated with AME, orally for 5 consecutive days (as in Group-II), and were exposed to gamma radiation half an hour after the last administration of AME on day 5. Animals from all these group autopsied on 12 hrs, days 1, 3, 7, 15 and 30 post-treatment intervals

  5. Radiation-induced recurrent intestinal pseudo-obstruction

    International Nuclear Information System (INIS)

    Conklin, J.L.; Anuras, S.

    1981-01-01

    The syndrome of intestinal pseudo-obstruction is a complex of signs and symptoms of intestinal obstruction without evidence of mechanical obstruction of the intestinal lumen. A patient with radiation-induced intestinal pseudoobstruction is described. The patient is a 74-year old woman with a history of chronic diarrhea, recurrent episodes of crampy abdominal pain, nausea and vomiting since receiving a 13,000 rad radiation dose to the pelvis in 1954. She has been hospitalized on many occasions for symptoms and signs of bowel obstruction. Upper gastrointestinal contrast roentgenograms with small bowel follow-through done during these episodes revealed multiple dilated loops of small bowel with no obstructing lesion. Barium enemas revealed no obstructing lesion. Each episode resolved with conservative therapy. Other secondary causes for intestinal pseudo-obstruction were ruled out in our patient. She gave no history of familial gastrointestinal disorders. Although postirradiation motility abnormalities have been demonstrated experimentally this is the first report of radiation induced intestinal pseudo-obstruction

  6. Mucus reduction promotes acetyl salicylic acid-induced small intestinal mucosal injury in rats.

    Science.gov (United States)

    Suyama, Yosuke; Handa, Osamu; Naito, Yuji; Takayama, Shun; Mukai, Rieko; Ushiroda, Chihiro; Majima, Atsushi; Yasuda-Onozawa, Yuriko; Higashimura, Yasuki; Fukui, Akifumi; Dohi, Osamu; Okayama, Tetsuya; Yoshida, Naohisa; Katada, Kazuhiro; Kamada, Kazuhiro; Uchiyama, Kazuhiko; Ishikawa, Takeshi; Takagi, Tomohisa; Konishi, Hideyuki; Itoh, Yoshito

    2018-03-25

    Acetyl salicylic acid (ASA) is a useful drug for the secondary prevention of cerebro-cardiovascular diseases, but it has adverse effects on the small intestinal mucosa. The pathogenesis and prophylaxis of ASA-induced small intestinal injury remain unclear. In this study, we focused on the intestinal mucus, as the gastrointestinal tract is covered by mucus, which exhibits protective effects against various gastrointestinal diseases. ASA was injected into the duodenum of rats, and small intestinal mucosal injury was evaluated using Evans blue dye. To investigate the importance of mucus, Polysorbate 80 (P80), an emulsifier, was used before ASA injection. In addition, rebamipide, a mucus secretion inducer in the small intestine, was used to suppress mucus reduction in the small intestine of P80-administered rats. The addition of P80 reduced the mucus and exacerbated the ASA-induced small intestinal mucosal injury. Rebamipide significantly suppressed P80-reduced small intestinal mucus and P80-increased intestinal mucosal lesions in ASA-injected rats, demonstrating that mucus is important for the protection against ASA-induced small intestinal mucosal injury. These results provide new insight into the mechanism of ASA-induced small intestinal mucosal injury. Mucus secretion-increasing therapy might be useful in preventing ASA-induced small intestinal mucosal injury. Copyright © 2018 Elsevier Inc. All rights reserved.

  7. The Effect of DA-6034 on Intestinal Permeability in an Indomethacin-Induced Small Intestinal Injury Model.

    Science.gov (United States)

    Kwak, Dong Shin; Lee, Oh Young; Lee, Kang Nyeong; Jun, Dae Won; Lee, Hang Lak; Yoon, Byung Chul; Choi, Ho Soon

    2016-05-23

    DA-6034 has anti-inflammatory activities and exhibits cytoprotective effects in acute gastric injury models. However, explanations for the protective effects of DA-6034 on intestinal permeability are limited. This study sought to investigate the effect of DA-6034 on intestinal permeability in an indomethacin-induced small intestinal injury model and its protective effect against small intestinal injury. Rats in the treatment group received DA-6034 from days 0 to 2 and indomethacin from days 1 to 2. Rats in the control group received indomethacin from days 1 to 2. On the fourth day, the small intestines were examined to compare the severity of inflammation. Intestinal permeability was evaluated by using fluorescein isothiocyanate-labeled dextran. Western blotting was performed to confirm the association between DA-6034 and the extracellular signal-regulated kinase (ERK) pathway. The inflammation scores in the treatment group were lower than those in the control group, but the difference was statistically insignificant. Hemorrhagic lesions in the treatment group were broader than those in the control group, but the difference was statistically insignificant. Intestinal permeability was lower in the treatment group than in the control group. DA-6034 enhanced extracellular signal-regulated kinase expression, and intestinal permeability was negatively correlated with ERK expression. DA-6034 may decrease intestinal permeability in an indomethacin-induced intestinal injury model via the ERK pathway.

  8. Bovine colostrum improves intestinal function following formula-induced gut inflammation in preterm pigs

    DEFF Research Database (Denmark)

    Støy, Ann Cathrine Findal; Heegaard, Peter M. H.; Thymann, Thomas

    2014-01-01

    Background & aims Only few hours of formula feeding may induce proinflammatory responses and predispose to necrotizing enterocolitis (NEC) in preterm pigs. We hypothesized that bovine colostrum, rich in bioactive factors, would improve intestinal function in preterm pigs following an initial...... exposure to formula feeding after some days of total parenteral nutrition (TPN). Methods After receiving TPN for 2 days, preterm pigs were fed formula (FORM, n = 14), bovine colostrum (COLOS, n = 6), or formula (6 h) followed by bovine colostrum (FCOLOS, n = 14). Intestinal lesions, function, and structure...... and FCOLOS pigs, relative to FORM pigs. Intestinal gene expression of serum amyloid A, IL-1β, -6 and -8, and bacterial abundance, correlated positively with NEC severity of the distal small intestine. Conclusions Bovine colostrum restores intestinal function after initial formula-induced inflammation...

  9. Gastric intestinal metaplasia: an intermediate precancerous lesion in the cascade of gastric carcinogenesis

    International Nuclear Information System (INIS)

    Malik, T.H.; Hong, X.; Sayahan, M.Y.A.

    2017-01-01

    Gastric intestinal metaplasia, an intermediate lesion in the development of intestinal-type gastric cancer, is observed in the milieu of long standing non-atrophic gastritis and atrophic gastritis. Most patients with intestinal metaplasia remain asymptomatic unless cobalamin deficiency occurs secondary to loss of glands (that produce intrinsic factor and acid). Genetic events that predispose to development of gastric intestinal metaplasia remains an enigma. Mechanisms leading to the progression of atrophy to metaplasia still needs to be comprehensively explored. Many studies in the literature describe a positive effect of typing intestinal metaplasia and concluded that intestinal metaplasia type III carries the highest risk for developing gastric cancer while others refute it. It is well established that Helicobacter pylori infection is the most important factor for the development of chronic gastritis, gastric intestinal metaplasia as well as gastric cancer. Countries with a higher prevalence of Helicobacter pylori infection and gastric cancer also have a high tendency of being prevalent for intestinal metaplasia. However, it remains elusive whether eradication of Helicobacter pylori infection tends to regress gastric intestinal metaplasia or reduce the subsequent risk of cancer development. Putting together, more prospective cohort studies should be designed to identify factors (antioxidants; anti-inflammatory drugs; food therapy) that may contribute in the regression of intestinal metaplasia, when used simultaneously with eradication therapy. Furthermore, molecular markers for evaluation of intestinal metaplasia, and the potential point-of-no-return should be further investigated. Consensus is also required to advocate a timeframe for surveillance of patients with gastric intestinal metaplasia. (author)

  10. Histomorphometry and macroscopic intestinal lesions in broilers infected with Eimeria acervulina.

    Science.gov (United States)

    Assis, R C L; Luns, F D; Beletti, M E; Assis, R L; Nasser, N M; Faria, E S M; Cury, M C

    2010-03-25

    This study aimed at measuring intestinal villi and assessing the intestinal absorptive area in broilers infected with Eimeria acervulina under different treatments to control coccidiosis. The experiment was divided into two stages, carried out in successive housings, raised in the same environment (or aviary). In the first stage, on 25 May 2008, fifty 12-day-old birds were orally inoculated with 3 x 10(3) oocysts of E. acervulina. In the second stage, on July 2008, other 50 birds were allocated on litter contaminated by the feces of birds on the first housing (natural infection by oocysts present in the reused litter). The experiment was arranged in a complete randomized design with five treatments and three replicates of 10 chicks per treatment. Broiler chicks were housed at 1 day of age and autopsies were performed at 21 days of age. Three 2-cm-long segments of the duodenum were excised from each bird and fixed in 10% buffered formalin. A total of 30 slides were prepared for each treatment, totaling 150 evaluated histological sections using H&E staining. Villus morphology was carried out by the HL Image 97 software. The intestinal absorptive area was calculated and macroscopic lesions were classified according to standard lesion scores. Results showed that intestinal villus measurements and absorptive area are directly affected by E. acervulina and that there is direct and positive correlation between the macro and microscopic findings observed in intestinal coccidiosis. E. acervulina causes shortening of villi and reduction in the intestinal absorptive area, affecting broiler growth. The prevention method of litter fermentation during the interval between housings and oral administration of Diclazuril can reduce the severity of intestinal lesions by E. acervulina in broilers impairing oocyst virulence or viability.

  11. Benign Lesions in Mucosa Adjacent to Intestinal-Type Sinonasal Adenocarcinoma

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    Blanca Vivanco

    2011-01-01

    Full Text Available Occupational exposure to wood dust is a strong risk factor for the development of intestinal-type sinonasal adenocarcinoma (ITAC; however, knowledge on possible precursor lesions or biomarkers is limited. Fifty-one samples of tumor-adjacent mucosa and 19 control samples of mucosa from the unaffected fossa of ITAC patients were evaluated for histological changes and p53 protein expression. Mild dysplasia was observed in 14%, cuboidal metaplasia in 57%, intestinal metaplasia in 8%, squamous metaplasia in 24%, and cylindrocellular hyperplasia in 53% of cases. P53 immunopositivity was generally weak occurring most frequently in squamous metaplasia. Wood dust etiology did not appear of influence on the histological changes, but p53 showed a tendency for higher positivity. Dysplasia adjacent to tumor was indicative of subsequent development of recurrence. In conclusion, precursor lesions do occur in mucosa adjacent to ITAC. This is clinically important, because it may justify the screening of high-risk individuals such as woodworkers.

  12. Radiation-induced lesions of the aorta

    Energy Technology Data Exchange (ETDEWEB)

    Doessing, M; Rasmussen, S [Medical Department C, Diakonissestiftelsen, Copenhagen (Denmark); Fischer-Hansen, B; Walbom-Joergensen, S

    1977-04-09

    A description is given of pathological changes detected in the aortic arch of a 21-year-old man. The patient died from an acute myocardial infarction 16 months after a dose of 3696 rads to a mantle field for Hodgkin's disease confined to the midcervical lymph nodes on the left side of the neck. Histological examination of the exposed part of the aortic arch showed the wall to be focally thickened owing to a pronounced fibrosis of the luminal third of the wall. The elastic lamellae in this area were reduced in number, broken up, and haphazardly arranged. The intima appeared normal. There was no leucocytic infiltration, no proliferation of vasa vasorum and no significant adventitial fibrosis. It is suggested that these noncharacteristic changes may have been early radiation-induced lesions which later might induce fibrotic scarring with perhaps clinically evident disease.

  13. A report of unusual diffuse nodular lesions in intestines of lambs with coccidiosis

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    a.r Taghavi Razavizadeh

    2016-11-01

    Full Text Available Ovine and caprine coccidiosis has always been regarded as one of the important diseases with high morbidity and economic losses such as weight loss, death and costs of treatment and control. In a sheep farm, 4 sick newborn lambs (out of 10 lambs with the age of 1 to 2 months died with clinical signs of weight loss, loss of appetite, yellowish diarrhea, fever, ruffled wool, contamination of tail and perineal area to diarrheic stool and abdominal pain at the touch of abdomen. At necropsy on one lamb, multiple and diffuse nodular hyperplastic lesions yellowish-white in color were seen in the mucosal surface of jejunum. Microscopically, in addition to hyperplasia of the small intestinal villi, various developmental stages of Eimeria were observed. Based on morphological characteristics and presence of numerous polyp like formations in small intestine, the involved protozoan species was determined as Eimeria bakuensis. The relatively high case fatality rate in this flock could be related to sever nodular lesions in the small intestines, age and immune status of the affected animals.

  14. Introducing enteral feeding induces intestinal subclinical inflammation and respective chromatin changes in preterm pigs

    DEFF Research Database (Denmark)

    Willems, Rhea; Krych, Lukasz; Rybicki, Verena

    2015-01-01

    AIM: To analyze how enteral food introduction affects intestinal gene regulation and chromatin structure in preterm pigs. MATERIALS & METHODS: Preterm pigs were fed parenteral nutrition plus/minus slowly increasing volumes of enteral nutrition. Intestinal gene-expression and chromatin structure......; no significant differences for colostrum) with corresponding decondensed chromatin configurations. On histology this correlated with mild mucosal lesions, particularly in formula-fed pigs. In CaCo-2 cells, histone hyperacetylation led to a marked increase in TLR4 mRNA and increased IL8 expression upon...... stimulation with lipopolysaccharide (median: 7.0; interquartile range: 5.63-8.85) compared with naive cells (median 4.2; interquartile range: 2.45-6.33; p = 0.03). CONCLUSION: Enteral feeding, particular with formula, induces subclinical inflammation in the premature intestine and more open chromatin...

  15. St. John's wort attenuates irinotecan-induced diarrhea via down-regulation of intestinal pro-inflammatory cytokines and inhibition of intestinal epithelial apoptosis

    International Nuclear Information System (INIS)

    Hu Zeping; Yang Xiaoxia; Chan Suiyung; Xu Anlong; Duan Wei; Zhu Yizhun; Sheu, F.-S.; Boelsterli, Urs Alex; Chan, Eli; Zhang Qiang; Wang, J.-C.; Ee, Pui Lai Rachel; Koh, H.L.; Huang Min; Zhou Shufeng

    2006-01-01

    Diarrhea is a common dose-limiting toxicity associated with cancer chemotherapy, in particular for drugs such as irinotecan (CPT-11), 5-fluouracil, oxaliplatin, capecitabine and raltitrexed. St. John's wort (Hypericum perforatum, SJW) has anti-inflammatory activity, and our preliminary study in the rat and a pilot study in cancer patients found that treatment of SJW alleviated irinotecan-induced diarrhea. In the present study, we investigated whether SJW modulated various pro-inflammatory cytokines including interleukins (IL-1β, IL-2, IL-6), interferon (IFN-γ) and tumor necrosis factor-α (TNF-α) and intestinal epithelium apoptosis in rats. The rats were treated with irinotecan at 60 mg/kg for 4 days in combination with oral SJW or SJW-free control vehicle at 400 mg/kg for 8 days. Diarrhea, tissue damage, body weight loss, various cytokines including IL-1β, IL-2, IL-6, IFN-γ and TNF-α and intestinal epithelial apoptosis were monitored over 11 days. Our studies demonstrated that combined SJW markedly reduced CPT-11-induced diarrhea and intestinal lesions. The production of pro-inflammatory cytokines such as IL-1β, IFN-γ and TNF-α was significantly up-regulated in intestine. In the mean time, combined SJW significantly suppressed the intestinal epithelial apoptosis induced by CPT-11 over days 5-11. In particular, combination of SJW significantly inhibited the expression of TNF-α mRNA in the intestine over days 5-11. In conclusion, inhibition of pro-inflammatory cytokines and intestinal epithelium apoptosis partly explained the protective effect of SJW against the intestinal toxicities induced by irinotecan. Further studies are warranted to explore the potential for STW as an agent in combination with chemotherapeutic drugs to lower their dose-limiting toxicities

  16. Milk diets influence doxorubicin-induced intestinal toxicity in piglets

    DEFF Research Database (Denmark)

    Shen, R. L.; Pontoppidan, P. E.; Rathe, M.

    2016-01-01

    Chemotherapy-induced gastrointestinal (GI) toxicity is a common adverse effect of cancer treatment. We used preweaned piglets as models to test our hypothesis that the immunomodulatory and GI trophic effects of bovine colostrum would reduce the severity of GI complications associated with doxorub......Chemotherapy-induced gastrointestinal (GI) toxicity is a common adverse effect of cancer treatment. We used preweaned piglets as models to test our hypothesis that the immunomodulatory and GI trophic effects of bovine colostrum would reduce the severity of GI complications associated...... to assess markers of small intestinal function and inflammation. All DOX-treated animals developed diarrhea, growth deficits, and leukopenia. However, the intestines of DOX-Colos pigs had lower intestinal permeability, longer intestinal villi with higher activities of brush border enzymes, and lower tissue...

  17. Precision cut intestinal slices are an appropriate ex vivo model to study NSAID-induced intestinal toxicity in rats

    NARCIS (Netherlands)

    Niu, Xiaoyu; de Graaf, Inge A. M.; van der Bij, Hendrik A.; Groothuis, Geny M. M.

    2014-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used therapeutic agents, however, they are associated with a high prevalence of intestinal side effects. In this investigation, rat precision cut intestinal slices (PCIS) were evaluated as an ex vivo model to study NSAID-induced intestinal

  18. Curcumin Attenuates Gamma Radiation Induced Intestinal Damage in Rats

    International Nuclear Information System (INIS)

    EI-Tahawy, N.A.

    2009-01-01

    Small Intestine exhibits numerous morphological and functional alterations during radiation exposure. Oxidative stress, a factor implicated in the intestinal injury may contribute towards some of these alterations. The present work was designed to evaluate the efficacy of curcumin, a yellow pigment of turmeric on y-radiation-induced oxidative damage in the small intestine by measuring alterations in the level of thiobarbituric acid reactive substances (TSARS), serotonin metabolism, catecholamine levels, and monoamine oxidase (MAO) activity in parallel to changes in the architecture of intestinal tissues. In addition, monoamine level, MAO activity and TSARS level were determined in the serum. Curcumin was supplemented orally via gavages, to rats at a dose of (45 mg/ Kg body wt/ day) for 2 weeks pre-irradiation and the last supplementation was 30 min pre exposure to 6.5 Gy gamma radiations (applied as one shot dose). Animals were sacrificed on the 7th day after irradiation. The results demonstrated that, whole body exposure of rats to ionizing radiation has induced oxidative damage in small intestine obvious by significant increases of TSARS content, MAO activity and 5-hydroxy indole acetic acid (5-HIAA) and by significant decreases of serotonin (5-HT), dopamine (DA), norepinephrine (NE) and epinephrine (EPI) levels. In parallel histopathological studies of the small intestine of irradiated rats through light microscopic showed significant decrease in the number of villi, villus height, mixed sub mucosa layer with more fibres and fibroblasts. Intestinal damage was in parallel to significant alterations of serum MAO activity, TBARS, 5-HT, DA, NE and EPI levels. Administration of curcumin before irradiation has significantly improved the levels of monoamines in small intestine and serum of irradiated rats, which was associated with significant amelioration in MAO activity and TBARS contents

  19. Relation between radiation-induced tissue injury and its carcinogenesis of the rat small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Tsubouchi, S [Aichi Cancer Center, Nagoya (Japan). Research Inst.; Matsuzawa, T

    1975-06-01

    This study was undertaken to make clear the relationships between radiation-induced tissue injury and its carcinogenesis in the rat small intestine. The abdomens of Wistar rats were irradiated locally with 1000 to 2000 rads. Approximately 2 months following irradiation, visible nodules were found in the intestines of the groups receiving irradiation. Nodule incidence was 80 to 100% in groups that received 1750 or 2000 rads, 50% in the 1500-rad groups, and 3% in the 1000-rad groups, respectively. The histology of the nodules within 70 days postirradiation, revealed adenomatous hyperplasia, including invasion of submucosa, muscle layers, and serosa of the small intestine accompanied by an area of fibrous tissue resulting from desmoplastic reaction by irradiation injury. The nodule within 140 to 300 days postirradiation induced advanced tissue injuried, that is, a polypoid lesion in histology and intestinal nodular adhesion in macroscopic anatomy. Running parallel with the advance of the above mentioned tissue injuries, the nodules in 3 out of 18 rat during 200 to 300 days postirradiation showed mucoid adenocarcinoma.

  20. Relation between radiation-induced tissue injury and its carcinogenesis of the rat small intestine

    International Nuclear Information System (INIS)

    Tsubouchi, Susumu; Matsuzawa, Taiju.

    1975-01-01

    This study was undertaken to make clear the relationships between radiation-induced tissue injury and its carcinogenesis in the rat small intestine. The abdomens of Wistar rats were irradiated locally with 1000 to 2000 rads. Approximately 2 months following irradiation, visible nodules were found in the intestines of the groups receiving irradiation. Nodule incidence was 80 to 100% in groups that received 1750 or 2000 rads, 50% in the 1500-rad groups, and 3% in the 1000-rad groups, respectively. The histology of the nodules within 70 days postirradiation, revealed adenomatous hyperplasia, including invasion of submucosa, muscle layers, and serosa of the small intestine accompanied by an area of fibrous tissue resulting from desmoplastic reaction by irradiation injury. The nodule within 140-300 days postirradiation induced advanced tissue injuried, that is, a polypoid lesion in histology and intestinal nodular adhesion in macroscopic anatomy. Running parallel with the advance of the above mentioned tissue injuries, the nodules in 3 out of 18 rat during 200-300 days postirradiation showed mucoid adenocarcinoma. (author)

  1. Dextran sodium sulfate (DSS induces necrotizing enterocolitis-like lesions in neonatal mice.

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    Marco Ginzel

    Full Text Available Necrotizing enterocolitis (NEC is an inflammatory bowel disease of preterm human newborns with yet unresolved etiology. An established neonatal murine model for NEC employs oral administration of lipopolysaccharides (LPS combined with hypoxia/hypothermia. In adult mice, feeding dextran sodium sulfate (DSS represents a well-established model for experimental inflammatory bowel disease. Here we investigated the effect of DSS administration on the neonatal murine intestine in comparison with the established NEC model.3-day-old C57BL/6J mice were either fed formula containing DSS or LPS. LPS treated animals were additionally stressed by hypoxia/hypothermia twice daily. After 72 h, mice were euthanized, their intestinal tissue harvested and analyzed by histology, qRT-PCR and flow cytometry. For comparison, adult C57BL/6J mice were fed with DSS for 8 days and examined likewise. Untreated, age matched animals served as controls.Adult mice treated with DSS exhibited colonic inflammation with significantly increased Cxcl2 mRNA expression. In contrast, tissue inflammation in neonatal mice treated with DSS or LPS plus hypoxia/hypothermia was present in colon and small intestine as well. Comparative analysis of neonatal mice revealed a significantly increased lesion size and intestinal Cxcl2 mRNA expression after DSS exposure. Whereas LPS administration mainly induced local neutrophil recruitment, DSS treated animals displayed increased monocytes/macrophages infiltration.Our study demonstrates the potential of DSS to induce NEC-like lesions accompanied by a significant humoral and cellular immune response in the small and large intestine of neonatal mice. The new model therefore represents a good alternative to LPS plus hypoxia/hypothermia administration requiring no additional physical stress.

  2. Review of Atrophic Gastritis and Intestinal Metaplasia as a Premalignant Lesion of Gastric Cancer

    Science.gov (United States)

    Park, Yo Han; Kim, Nayoung

    2015-01-01

    Atrophic gastritis (AG) and intestinal metaplasia (IM) are the main precursor lesions of gastric cancer as the incidence of gastric cancer increases in the gastric mucosa involved with AG and IM. The prevalence of AG and IM vary depending on countries, even it represents diverse results in the same nation. Usually AG is antecedent of IM but the etiologies of AG and IM are not always the same. The sensitivity and specificity of diagnostic methods to detect AG and IM are different. Furthermore, the management strategy of AG and IM has not been established, yet. Helicobacter pylori infection has been proved as the most important cause of AG and IM. Thus the eradication of H. pylori is very important to prevent the progression to gastric cancer which is still placed in the high rank in morbidity and mortality among cancers. However, the reversibility of AG and IM by eradication of H. pylori which was assumed to be certain by meta-analysis is; however, controversial now. Therefore, the understanding and early diagnosis of AG and IM are very important, especially, in high incidence area of gastric cancer such as Republic of Korea. PMID:25853101

  3. Milk diets influence doxorubicin-induced intestinal toxicity in piglets

    DEFF Research Database (Denmark)

    Shen, R. L.; Pontoppidan, P. E.; Rathe, M.

    2016-01-01

    IL-8 levels compared with DOX-Form (all P diet. Thus a single dose of DOX induces intestinal toxicity in preweaned pigs...... and may lead to a systemic inflammatory response. The toxicity is affected by type of enteral nutrition with more pronounced GI toxicity when formula is fed compared with bovine colostrum. The results indicate that bovine colostrum may be a beneficial supplementary diet for children subjected...

  4. Effects of corn oil administered orally on conspicuity of ultrasonographic small intestinal lesions in dogs with lymphangiectasia.

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    Pollard, Rachel E; Johnson, Eric G; Pesavento, Patricia A; Baker, Tomas W; Cannon, Allison B; Kass, Philip H; Marks, Stanley L

    2013-01-01

    Lymphangiectasia is one of the causes of protein-losing enteropathy in dogs and characteristic ultrasonographic small intestinal lesions have been previously described. The purpose of this study was to determine whether corn oil administered orally (COAO) would result in increased conspicuity of these characteristic small intestinal ultrasonographic lesions in dogs with lymphangiectasia. Affected dogs were included if they underwent corn oil administered orally and had a surgical full-thickness intestinal biopsy diagnosis of lymphangiectasia. Control dogs had normal clinical examination and standard laboratory test findings. Ultrasound images of duodenum, jejunum, and ileum were obtained prior to and 30, 60, 90, and 120 min after corn oil administered orally for all dogs. Parameters recorded for each ultrasound study were intestinal wall thickness, mucosal echogenicity, and presence or absence of hyperechoic mucosal striations (HMS) and a parallel hyperechoic mucosal line (PHML). Nine affected and five controls dogs were included in the study. Seven of the nine dogs with lymphangiectasia had hyperechoic mucosal striations prior to corn oil administered orally. Jejunal hyperechoic mucosal striations were significantly associated with lymphangiectasia at multiple time points (P dogs with lymphangiectasia 60 or 90 min after corn oil administered orally. Increased mucosal echogenicity was observed in all dogs at multiple time points after corn oil administered orally. A parallel hyperechoic mucosal line was present in the jejunum in 4/5 healthy and 6/9 dogs with lymphangiectasia at one or more time points after corn oil administered orally. Findings indicated that corn oil administered orally improves conspicuity of characteristic ultrasonographic lesions in dogs with lymphangiectasia, however some of these lesions may also be present in healthy dogs that recently received a fatty meal. © 2013 Veterinary Radiology & Ultrasound.

  5. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    International Nuclear Information System (INIS)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G.; Castiglione, F.; Vanzi, E.; Bottoncetti, A.; Pupi, A.

    2011-01-01

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation-induced

  6. Rosiglitazone attenuates pulmonary fibrosis and radiation-induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Mangoni, M.; Gerini, C.; Sottili, M.; Cassani, S.; Stefania, G.; Biti, G. [Radiotherapy Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy); Castiglione, F. [Department of Human Pathology and Oncology, University of Florence, Firenze (Italy); Vanzi, E.; Bottoncetti, A.; Pupi, A. [Nuclear Medicine Unit, Clinical Physiopathology Department, University of Florence, Firenze (Italy)

    2011-10-15

    Full text of publication follows: Purpose.-The aim of the study was to evaluate radioprotective effect of rosiglitazone (RGZ) on a murine model of late pulmonary damage and of acute intestinal damage. Methods.- Lung fibrosis: C57 mice were treated with the radiomimetic agent bleomycin, with or without rosiglitazone (5 mg/kg/day). To obtain an independent qualitative and quantitative measure for lung fibrosis we used high resolution CT, performed twice a week during the entire observation period. Hounsfield Units (HU) of section slides from the upper and lower lung region were determined. On day 31 lungs were collected for histological analysis. Acute intestinal damage: mice underwent 12 Gy total body irradiation with or without rosiglitazone. Mice were sacrificed 24 or 72 h after total body irradiation and ileum and colon were collected. Results.- Lung fibrosis: after bleomycin treatment, mice showed typical CT features of lung fibrosis, including irregular septal thickening and patchy peripheral reticular abnormalities. Accordingly, HU lung density was dramatically increased. Rosiglitazone markedly attenuated the radiological signs of fibrosis and strongly inhibited HU lung density increase (60% inhibition at the end of the observation period). Histological analysis revealed that in bleomycin-treated mice, fibrosis involved 50-55% of pulmonary parenchyma and caused an alteration of the alveolar structures in 10% of parenchyma, while in rosiglitazone-treated mice, fibrosis involved only 20-25% of pulmonary parenchyma, without alterations of the alveolar structures. Acute intestinal damage: 24 h after 12 Gy of total body irradiation intestinal mucosa showed villi shortening, mucosal thickness and crypt necrotic changes. Rosiglitazone showed a histological improvement of tissue structure, with villi and crypts normalization and oedema reduction. Conclusion.- These results demonstrate that rosiglitazone displays a protective effect on pulmonary fibrosis and radiation-induced

  7. Radioprotective effects of sodium arginate on radiation induced intestinal damage

    Energy Technology Data Exchange (ETDEWEB)

    Nakatsugawa, Shigekazu; Yukawa, Yutaka; Abe, Mitsuyuki.

    1988-05-01

    Effects of sodium arginate were examined on radiation-induced intestinal death of mice and on the pathological changes of the ileum after whole or partial abdominal X-irradiation. BALB/c male mice (SPF, 7 approx. 8 week old, 21 approx. 28 g body weight) were irradiated with various doses of 10 MV of X-rays under general anesthesia (dose rate : 4 Gy/min). A radiation field covers either 2.5 or 5.0 cm width of abdomen from the anus. Sterilized water or 5 % sodium arginate solution (0.2 ml/body) was daily given per os through a stomach tube until the death of mice or 15 approx. 21 days after X-ray exposure. Intestinal death was examined daily. In another experiment, mice were daily sacrificed and pathological specimens were made. In order to study the effects of sodium arginate on peripheral blood circulation in the ileum after X-ray exposure, the microangiograms with Ba contrast media were also taken. Sodium arginate showed statistically significant radioprotective effects on intestinal death after 14.5 approx. 15.0 Gy of X-ray irradiation to the abdomen through a radiation field of 5.0 cm width or after 18.0 Gy of X-irradiation to the abdomen through a field of 2.5 cm width. The pathological studies suggest that the drug may protect the surface of the intestine against infection and potentiate the recovery processes of the mucosal membrane. This may elucidate the possible mechanisms of radioprotective effects of sodium arginate on esophagitis or on rectal ulcer induced by radiotherapy.

  8. Photothermal lesions in soft tissue induced by optical fiber microheaters.

    Science.gov (United States)

    Pimentel-Domínguez, Reinher; Moreno-Álvarez, Paola; Hautefeuille, Mathieu; Chavarría, Anahí; Hernández-Cordero, Juan

    2016-04-01

    Photothermal therapy has shown to be a promising technique for local treatment of tumors. However, the main challenge for this technique is the availability of localized heat sources to minimize thermal damage in the surrounding healthy tissue. In this work, we demonstrate the use of optical fiber microheaters for inducing thermal lesions in soft tissue. The proposed devices incorporate carbon nanotubes or gold nanolayers on the tips of optical fibers for enhanced photothermal effects and heating of ex vivo biological tissues. We report preliminary results of small size photothermal lesions induced on mice liver tissues. The morphology of the resulting lesions shows that optical fiber microheaters may render useful for delivering highly localized heat for photothermal therapy.

  9. Radiation-induced vascular lesions of the skin: an overview

    NARCIS (Netherlands)

    Flucke, U.E.; Requena, L.; Mentzel, T.

    2013-01-01

    Radiation-induced cutaneous vascular neoplasms occur infrequently and comprise benign, so-called atypical vascular lesions (AVL) and angiosarcomas (AS), often being high-grade malignant tumors. Both arise most frequently within previously irradiated skin in breast-conserving-treated mammary cancer

  10. Effects of Diclofenac, L-NAME, L-Arginine, and Pentadecapeptide BPC 157 on Gastrointestinal, Liver, and Brain Lesions, Failed Anastomosis, and Intestinal Adaptation Deterioration in 24 Hour-Short-Bowel Rats.

    Science.gov (United States)

    Lojo, Nermin; Rasic, Zarko; Zenko Sever, Anita; Kolenc, Danijela; Vukusic, Darko; Drmic, Domagoj; Zoricic, Ivan; Sever, Marko; Seiwerth, Sven; Sikiric, Predrag

    2016-01-01

    Stable gastric pentadecapeptide BPC 157 was previously used to ameliorate wound healing following major surgery and counteract diclofenac toxicity. To resolve the increasing early risks following major massive small bowel resectioning surgery, diclofenac combined with nitric oxide (NO) system blockade was used, suggesting therapy with BPC 157 and the nitric oxide synthase (NOS substrate) L-arginine, is efficacious. Immediately after anastomosis creation, short-bowel rats were untreated or administered intraperitoneal diclofenac (12 mg/kg), BPC 157 (10 μg/kg or 10 ng/kg), L-NG-nitroarginine methyl ester (L-NAME, 5 mg/kg), L-arginine (100 mg/kg) alone or combined, and assessed 24 h later. Short-bowel rats exhibited poor anastomosis healing, failed intestine adaptation, and gastrointestinal, liver, and brain lesions, which worsened with diclofenac. This was gradually ameliorated by immediate therapy with BPC 157 and L-arginine. Contrastingly, NOS-blocker L-NAME induced further aggravation and lesions gradually worsened. Specifically, rats with surgery alone exhibited mild stomach/duodenum lesions, considerable liver lesions, and severe cerebral/hippocampal lesions while those also administered diclofenac showed widespread severe lesions in the gastrointestinal tract, liver, cerebellar nuclear/Purkinje cells, and cerebrum/hippocampus. Rats subjected to surgery, diclofenac, and L-NAME exhibited the mentioned lesions, worsening anastomosis, and macro/microscopical necrosis. Thus, rats subjected to surgery alone showed evidence of deterioration. Furtheremore, rats subjected to surgery and administered diclofenac showed worse symptoms, than the rats subjected to surgery alone did. Rats subjected to surgery combined with diclofenac and L-NAME showed the worst deterioration. Rats subjected to surgery exhibited habitual adaptation of the remaining small intestine, which was markedly reversed in rats subjected to surgery and diclofenac, and those with surgery, diclofenac, and

  11. New Neonatal Porcine Diarrhea Syndrome in Denmark Characterization of the intestinal lesions and identification of the etiology

    DEFF Research Database (Denmark)

    Jonach, Beata Renata; Jensen, Tim Kåre; Boye, Mette

    of various degrees with concomitant crypt hyperplasia in the jejunum and ileum (Chapter 4.1). Villus atrophy is a common pathological feature seen in numerous infectious intestinal conditions and is associated with malabsorptive diarrhea due to insufficient absorption of water and nutrients from the small...... with enlargement of the proliferative compartment in the crypts and that epithelial cell turnover was enhanced in the diarrheic piglets.Potentially pathogenic bacteria such as Escherichia coli, Enterococcus spp., Clostridium perfringens and Clostridium difficile have been proposed to be involved in NNPDS. In order...... that adherent E. coli and Enterococcus spp. were involved in NNPDS. These bacteria were present in 37% of the diarrheic piglets and were associated with villus atrophy and epithelial lesions in the small intestine. No clear association between the presence of C. perfringens and C. difficile and diarrhea...

  12. Present status and future view on virtual endoscopy. Depiction of minute lesions in the large intestine with CT colonography

    International Nuclear Information System (INIS)

    Sugino, Yoshinori

    2002-01-01

    CT colonography is a new imaging technique using helical CT. We studied the efficacy of CT colonoscopy in the detection of small polyps and depiction of superficial lesions. Concerning the detection of small polyps, we studied 54 patients with abnormality checked by barium enema. Conventional colonoscopy revealed 79 lesions (5 advanced carcinomas, 4 superficial-type adenomas and 70 polyps). CT colonography identified all 5 carcinomas, 3 of the 4 superficial lesions and 43 of the 45 polyps that were 0.5 cm or smaller in diameter, 18 of 22 polyps that were 0.6 to 0.9 cm, and all 3 polyps that were 1.0 cm or more in diameter. There were 92 false positive polyps that were 0.5 cm or smaller in diameter. On a superficial lesion, we could depict a superficial depressive type early colonic carcinoma 1.0 cm in diameter, using very thin-slice CT equipment. In conclusion, CT colonography has a high sensitivity for detection of small polyps and sufficient capability for depiction of superficial lesions. CT colonography may be suitable for screening examinations of the large intestine. (author)

  13. Inducible DNA-repair systems in yeast: competition for lesions.

    Science.gov (United States)

    Mitchel, R E; Morrison, D P

    1987-03-01

    DNA lesions may be recognized and repaired by more than one DNA-repair process. If two repair systems with different error frequencies have overlapping lesion specificity and one or both is inducible, the resulting variable competition for the lesions can change the biological consequences of these lesions. This concept was demonstrated by observing mutation in yeast cells (Saccharomyces cerevisiae) exposed to combinations of mutagens under conditions which influenced the induction of error-free recombinational repair or error-prone repair. Total mutation frequency was reduced in a manner proportional to the dose of 60Co-gamma- or 254 nm UV radiation delivered prior to or subsequent to an MNNG exposure. Suppression was greater per unit radiation dose in cells gamma-irradiated in O2 as compared to N2. A rad3 (excision-repair) mutant gave results similar to wild-type but mutation in a rad52 (rec-) mutant exposed to MNNG was not suppressed by radiation. Protein-synthesis inhibition with heat shock or cycloheximide indicated that it was the mutation due to MNNG and not that due to radiation which had changed. These results indicate that MNNG lesions are recognized by both the recombinational repair system and the inducible error-prone system, but that gamma-radiation induction of error-free recombinational repair resulted in increased competition for the lesions, thereby reducing mutation. Similarly, gamma-radiation exposure resulted in a radiation dose-dependent reduction in mutation due to MNU, EMS, ENU and 8-MOP + UVA, but no reduction in mutation due to MMS. These results suggest that the number of mutational MMS lesions recognizable by the recombinational repair system must be very small relative to those produced by the other agents. MNNG induction of the inducible error-prone systems however, did not alter mutation frequencies due to ENU or MMS exposure but, in contrast to radiation, increased the mutagenic effectiveness of EMS. These experiments demonstrate

  14. Role of intestinal bacteria in gliadin-induced changes in intestinal mucosa: study in germ-free rats.

    Directory of Open Access Journals (Sweden)

    Jana Cinova

    Full Text Available BACKGROUND AND AIMS: Celiac disease (CD is a chronic inflammatory disorder of the small intestine that is induced by dietary wheat gluten proteins (gliadins in genetically predisposed individuals. The overgrowth of potentially pathogenic bacteria and infections has been suggested to contribute to CD pathogenesis. We aimed to study the effects of gliadin and various intestinal bacterial strains on mucosal barrier integrity, gliadin translocation, and cytokine production. METHODOLOGY/PRINCIPAL FINDINGS: Changes in gut mucosa were assessed in the intestinal loops of inbred Wistar-AVN rats that were reared under germ-free conditions in the presence of various intestinal bacteria (enterobacteria and bifidobacteria isolated from CD patients and healthy children, respectively and CD-triggering agents (gliadin and IFN-γ by histology, scanning electron microscopy, immunofluorescence, and a rat cytokine antibody array. Adhesion of the bacterial strains to the IEC-6 rat cell line was evaluated in vitro. Gliadin fragments alone or together with the proinflammatory cytokine interferon (IFN-γ significantly decreased the number of goblet cells in the small intestine; this effect was more pronounced in the presence of Escherichia coli CBL2 and Shigella CBD8. Shigella CBD8 and IFN-γ induced the highest mucin secretion and greatest impairment in tight junctions and, consequently, translocation of gliadin fragments into the lamina propria. Shigella CBD8 and E. coli CBL2 strongly adhered to IEC-6 epithelial cells. The number of goblet cells in small intestine increased by the simultaneous incubation of Bifidobacterium bifidum IATA-ES2 with gliadin, IFN-γ and enterobacteria. B. bifidum IATA-ES2 also enhanced the production of chemotactic factors and inhibitors of metalloproteinases, which can contribute to gut mucosal protection. CONCLUSIONS: Our results suggest that the composition of the intestinal microbiota affects the permeability of the intestinal mucosa

  15. Elemental diets in the prophylaxis and therapy for intestinal lesions: an update

    International Nuclear Information System (INIS)

    Bounous, G.

    1989-01-01

    The recognition of potentially noxious physiologic substances in the intestinal milieu prompted the use of an elemental semihydrolyzed formula diet in the prophylaxis of experimental acute ischemic enteropathy. Elemental diets have been used in the management of a variety of digestive diseases. An elemental diet protects the intestinal mucosa of rodents from radiation injury and facilitates mucosal healing. Clinical trials have shown the benefits of this form of treatment in the prevention of acute radiation enteropathy and in the therapy for delayed radiation enteropathy and Crohn's disease.90 references

  16. Intestinal lesions in pediatric Crohn disease: comparative detectability among pulse sequences at MR enterography

    International Nuclear Information System (INIS)

    Sohn, Beomseok; Kim, Myung-Joon; Lee, Mi-Jung; Koh, Hong; Han, Kyung Hwa

    2014-01-01

    Variable sequences can be used in MR enterography, and no consensus exists for the best protocol in children with Crohn disease. To compare the lesion detectability of various MR enterography sequences and to correlate the findings of these sequences with the Pediatric Crohn's Disease Activity Index (PCDAI) in children with Crohn disease. Children with clinically or pathologically confirmed Crohn disease underwent MR enterography, including a single-shot fast spin-echo (SSFSE) sequence, motility imaging (coronal 2-D balanced fast field echo), diffusion-weighted imaging (DWI), and dynamic contrast enhancement imaging (including arterial, portal and delayed phases). The lesion detectability of each sequence was graded 0-2 for each involved bowel segment. The lesion detectability and PCDAI result on different sequences were compared using the weighted least squares method and Student's t-test, respectively. Fifteen children (11 boys, 4 girls, mean age 13.7 ± 1.4 years) with a total of 41 lesions were included in this study. All lesions detected in more than two sequences were visible on the single-shot fast spin-echo (SSFSE) sequence. The relative lesion detection rate was 78.1% on motility imaging, 90.2% on DWI, and 92.7% on arterial, 95.1% on portal and 95.1% on delayed phase imaging. Compared to the SSFSE sequence, motility imaging (P < 0.001) and DWI (P = 0.039) demonstrated lower detectability. The mean PCDAI result in the detected lesions was statistically higher only on dynamic enhancement imaging (P < 0.001). All MR enterography sequences were found to have relatively high lesion detectability in children with Crohn disease, while motility imaging showed the lowest lesion detectability. Lesions detected on dynamic enhancement imaging showed a higher PCDAI result, which suggests that this sequence is specific for active inflammation. (orig.)

  17. Food-grade TiO2 impairs intestinal and systemic immune homeostasis, initiates preneoplastic lesions and promotes aberrant crypt development in the rat colon.

    Science.gov (United States)

    Bettini, Sarah; Boutet-Robinet, Elisa; Cartier, Christel; Coméra, Christine; Gaultier, Eric; Dupuy, Jacques; Naud, Nathalie; Taché, Sylviane; Grysan, Patrick; Reguer, Solenn; Thieriet, Nathalie; Réfrégiers, Matthieu; Thiaudière, Dominique; Cravedi, Jean-Pierre; Carrière, Marie; Audinot, Jean-Nicolas; Pierre, Fabrice H; Guzylack-Piriou, Laurence; Houdeau, Eric

    2017-01-20

    Food-grade titanium dioxide (TiO 2 ) containing a nanoscale particle fraction (TiO 2 -NPs) is approved as a white pigment (E171 in Europe) in common foodstuffs, including confectionary. There are growing concerns that daily oral TiO 2 -NP intake is associated with an increased risk of chronic intestinal inflammation and carcinogenesis. In rats orally exposed for one week to E171 at human relevant levels, titanium was detected in the immune cells of Peyer's patches (PP) as observed with the TiO 2 -NP model NM-105. Dendritic cell frequency increased in PP regardless of the TiO 2 treatment, while regulatory T cells involved in dampening inflammatory responses decreased with E171 only, an effect still observed after 100 days of treatment. In all TiO 2 -treated rats, stimulation of immune cells isolated from PP showed a decrease in Thelper (Th)-1 IFN-γ secretion, while splenic Th1/Th17 inflammatory responses sharply increased. E171 or NM-105 for one week did not initiate intestinal inflammation, while a 100-day E171 treatment promoted colon microinflammation and initiated preneoplastic lesions while also fostering the growth of aberrant crypt foci in a chemically induced carcinogenesis model. These data should be considered for risk assessments of the susceptibility to Th17-driven autoimmune diseases and to colorectal cancer in humans exposed to TiO 2 from dietary sources.

  18. A Correlative Study of Smokeless Tobacco induced Lesion and Smoke-induced Leukoplakia in Various Aspects

    Directory of Open Access Journals (Sweden)

    Parita K Chitroda

    2011-01-01

    Full Text Available Various oral mucosal lesions are attributed to tobacco use. The presence of these conditions vanes with particular type of tobacco used (smoking or smokeless and the form in which it is used, such as cigarettes, pipes, cigars and chewing moist snuff. The frequency and duration of use as well as the ways in which the tobacco product is used also contributes to the clinical presentation and seventy of the lesion. The present study is mainly focused on the correlation between the smokeless tobacco-induced lesion and smoke-induced leukoplakia on various aspects with an objective to determine smokeless tobacco as a possible cause for leukoplakia.

  19. Ultrastructural apoptotic lesions induced in rat thymocytes after borax ingestion.

    Science.gov (United States)

    Sylvain, I C; Berry, J P; Galle, P

    1998-01-01

    Apoptosis has gained increasing attention in recent years. Several chemical compounds induce apoptotic lesions in the thymus. Male Wistar rats received 2000 ppm of borax (Na2B4O7.10H2O) in their food for 16 days. The rats were sacrificed 2, 5, 9, 12, 19, 21, 26 and 28 days after the beginning of treatment. Thymus samples of all rats were taken. A Philips EM 300 electron microscopy was used to study the ultrastructural morphology. Serious nuclear and cytoplasmic lesions were observed. Moreover, numerous macrophages containing apoptotic cells were present in the thymus. The alterations were observed from the 2nd to the 28th day. The extent of damage was much more important in the rats sacrificed 21, 26 and 28 days after borax ingestion.

  20. Antibiotic suppression of intestinal microbiota reduces heme-induced lipoperoxidation associated with colon carcinogenesis in rats.

    Science.gov (United States)

    Martin, O C B; Lin, C; Naud, N; Tache, S; Raymond-Letron, I; Corpet, D E; Pierre, F H

    2015-01-01

    Epidemiological studies show that heme iron from red meat is associated with increased colorectal cancer risk. In carcinogen-induced-rats, a heme iron-rich diet increases the number of precancerous lesions and raises associated fecal biomarkers. Heme-induced lipoperoxidation measured by fecal thiobarbituric acid reagents (TBARs) could explain the promotion of colon carcinogenesis by heme. Using a factorial design we studied if microbiota could be involved in heme-induced carcinogenesis, by modulating peroxidation. Rats treated or not with an antibiotic cocktail were given a control or a hemoglobin-diet. Fecal bacteria were counted on agar and TBARs concentration assayed in fecal water. The suppression of microbiota by antibiotics was associated with a reduction of crypt height and proliferation and with a cecum enlargement, which are characteristics of germ-free rats. Rats given hemoglobin diets had increased fecal TBARs, which were suppressed by the antibiotic treatment. A duplicate experiment in rats given dietary hemin yielded similar results. These data show that the intestinal microbiota is involved in enhancement of lipoperoxidation by heme iron. We thus suggest that microbiota could play a role in the heme-induced promotion of colorectal carcinogenesis.

  1. Ethanol induces rotational behavior in 6-hydroxydopamine lesioned mice

    Energy Technology Data Exchange (ETDEWEB)

    Silverman, P.B.

    1987-03-09

    Mice with unilateal striatal lesions created by 6-hydroxydopamine (6HDA) injection were screened for rotational (circling) behavior in response to injection of amphetamine and apomorphine. Those that rotated ipsilaterally in response to amphetamine and contralaterally in response to apomorphine were subsequently challenged with 1 to 3 g/kg (i.p.) ethanol. Surprisingly, ethanol induced dose related contralateral (apomorphine-like) rotation which, despite gross intoxication, was quite marked in most animals. No significant correlation was found between the number of turns made following ethanol and made after apomorphine or amphetamine. 14 references, 2 figures, 1 table.

  2. Endodontic periapical lesion-induced mental nerve paresthesia

    Science.gov (United States)

    Shadmehr, Elham; Shekarchizade, Neda

    2015-01-01

    Paresthesia is a burning or prickling sensation or partial numbness, resulting from neural injury. The symptoms can vary from mild neurosensory dysfunction to total loss of sensation in the innervated area. Only a few cases have described apical periodontitis to be the etiological factor of impaired sensation in the area innervated by the inferior alveolar and mental nerves. The aim of the present paper is to report a case of periapical lesion-induced paresthesia in the innervation area of the mental nerve, which was successfully treated with endodontic retreatment. PMID:25878687

  3. Modification of radiation-induced DNA lesions by oxygen

    International Nuclear Information System (INIS)

    Meyn, R.E.; Jenkins, W.T.

    1984-01-01

    The efficiency of DNA strand break production by radiation under aerated and hypoxic conditions was determined in CHO cells using the technique of alkaline elution. The resulting oxygen enhancement ratio was surprisingly high, 7.8. When the pH of the elution was increased from 12.1, the normally used pH, to 12.8, a substantial increase in the strand breaks produced in the hypoxic cells was observed, resulting in an OER of 4.8. This difference in susceptibility of DNA strand break detection as a function of pH suggested a difference in the type of lesions produced in DNA when irradiated under aerated and hypoxic conditions. Further experiments to examine the DNA-protein crosslinks produced by radiation suggested that the apparent lower level of strand breaks in hypoxic cells may be due to a higher level of DNA-protein crosslinks produced under hypoxic conditions. Thus, oxygen may not only act by modifying the quantity of radiation-induced DNA lesions but may also cause qualitative changes. If the different types of DNA lesions have different contributions to lethality, the OER for cell survival may represent a complex composite of these changes at the molecular level

  4. The role of metabolism in diclofenac-induced intestinal toxicity in rat and human in vitro

    NARCIS (Netherlands)

    Niu, Xiaoyu; Makkinje, Miriam; de Graaf, Inge; Groothuis, Genoveva

    The use of Diclofenac (DCF), a non-steroidal anti-inflammatory drug is associated with severe gastro-intestinal side-effects. The mechanisms of drug-induced intestinal toxicity are largely unknown due to the lack of in vitro models. In vivo rat studies suggested that reactive metabolites of DCF

  5. Effects of pregelatinized vs. native potato starch on intestinal weight and stomach lesions of pigs housed in barren pens or on straw bedding

    NARCIS (Netherlands)

    Bolhuis, J.E.; Brand, van den H.; Staals, S.; Gerrits, W.J.J.

    2007-01-01

    In a 2 × 2 factorial arrangement, 16 groups of 12 pigs (approximately 25 kg) were assigned to either barren or straw housing and to native or pregelatinized potato starch included in the diet (35%) to investigate effects on intestinal weight and gastric lesions. Pigs were fed restrictedly (2.5 ×

  6. Differences in the location and activity of intestinal Crohn's disease lesions between adult and paediatric patients detected with MRI

    International Nuclear Information System (INIS)

    Maccioni, Francesca; Carrozzo, Federica; Pino, Anna Rosaria; Staltari, Ilaria; Ansari, Najwa Al; Marini, Mario; Viola, Franca; Di Nardo, Giovanni; Cucchiara, Salvatore; Vestri, Annarita; Signore, Alberto

    2012-01-01

    To prospectively compare paediatric patients (PP) and adult patients (AP) affected by Crohn's disease (CD) in terms of the location and activity of intestinal lesions. Forty-three children (mean age 15 years) and 43 adults (mean age 48 years) with proven CD underwent magnetic resonance enterography (MRE) to localise lesions and detect their activity in 9 segments of the small and large bowel. The results were analysed on a per patient and per segment basis. Ileo-colonoscopy was performed in all patients. P values less than 0.05 were considered statistically significant. Involvement of terminal ileum was significantly different in the two groups: observed in 100 % of AP (43/43) versus 58 % (23/43) of PP (P < 0.0001). Conversely, the colon was diseased in 84 % of PP versus 64 % of AP. In particular, left colonic segments were significantly more involved in PP (descending colon 53 % versus 21 %, P < 0.01; rectum 67 % versus 23 %, P < 0.0001; sigmoid colon 56 % versus 37 %, not significant), whereas caecal involvement was equal in both groups. In children the maximal disease activity was found in left colonic segments, whereas in adults it was in the terminal ileum. MRE detected significant differences between the two populations, showing a more extensive and severe involvement of the left colon in children but the distal ileum in adults. (orig.)

  7. Intestinal metaplasia induced by x-irradiation in rat

    International Nuclear Information System (INIS)

    Watanabe, Hiromitsu; Terada, Yoritaka; Fujii, Isao; Yamamoto, Yukiko; Takizawa, Shoichi

    1978-01-01

    Total 400 rad of x-ray was given in 100 or 150 rad doses to the whole body of rats at intervals of one week, and one year and a half later, rats were killed. Disaccharidase was formed in most of animals, intestinal metaplasia only with goblet cells occurred in 65% of animals, and that with intestinal type of lacuna occurred in 36% of them. When 500 rad of x-ray was irradiated to each part of stomach day after day up to the total dose of 3,000 rad, biochemical intestinal metaplasia already occurred one week after the irradiation, and intestinal type lacuna occurred 2 months after the irradiation. Intestinal type lacuna was recognized in all animals killed 499 days after the irradiation, and intestinal metaplasia with Paneth's cells occurred in 6 out of 11 cases (56%). When a dose of 1,000 rad was irradiated to stomach three times at intervals of 2 days up to the total of 3,000 rad, much intestinal type lacuna was recognized 2 months after the irradiation, gastric adenoid cancerous changes appeared 4 months after, and gastric adenoid cancer occurred 6 months after. The above-mentioned results clarified that even if x-ray of a small dose was irradiated, intestinal metaplasia occurred, and that the period from the irradiation to occurrence of intestinal metaplasia was shortened by increasing a dose of x-ray. It was also clarified that not only intestinal metaplasia but also gastric adenoic cancer occurred due to a great amount of x-ray irradiation. (Ueda, J.)

  8. Intestinal metaplasia induced by x-irradiation in rat

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, H; Terada, Y; Fujii, I; Yamamoto, Y; Takizawa, S [Hiroshima Univ. (Japan). Research Inst. for Nuclear Medicine and Biology

    1978-04-01

    Total 400 rad of x-ray was given in 100 or 150 rad doses to the whole body of rats at intervals of one week, and one year and a half later, rats were killed. Disaccharidase was formed in most of animals, intestinal metaplasia only with goblet cells occurred in 65% of animals, and that with intestinal type of lacuna occurred in 36% of them. When 500 rad of x-ray was irradiated to each part of stomach day after day up to the total dose of 3,000 rad, biochemical intestinal metaplasia already occurred one week after the irradiation, and intestinal type lacuna occurred 2 months after the irradiation. Intestinal type lacuna was recognized in all animals killed 499 days after the irradiation, and intestinal metaplasia with Paneth's cells occurred in 6 out of 11 cases (56%). When a dose of 1,000 rad was irradiated to stomach three times at intervals of 2 days up to the total of 3,000 rad, much intestinal type lacuna was recognized 2 months after the irradiation, gastric adenoid cancerous changes appeared 4 months after, and gastric adenoid cancer occurred 6 months after. The above-mentioned results clarified that even if x-ray of a small dose was irradiated, intestinal metaplasia occurred, and that the period from the irradiation to occurrence of intestinal metaplasia was shortened by increasing a dose of x-ray. It was also clarified that not only intestinal metaplasia but also gastric adenoic cancer occurred due to a great amount of x-ray irradiation.

  9. Prophylactic Ozone Administration Reduces Intestinal Mucosa Injury Induced by Intestinal Ischemia-Reperfusion in the Rat

    Directory of Open Access Journals (Sweden)

    Ozkan Onal

    2015-01-01

    Full Text Available Objectives. Intestinal ischemia-reperfusion injury is associated with mucosal damage and has a high rate of mortality. Various beneficial effects of ozone have been shown. The aim of the present study was to show the effects of ozone in ischemia reperfusion model in intestine. Material and Method. Twenty eight Wistar rats were randomized into four groups with seven rats in each group. Control group was administered serum physiologic (SF intraperitoneally (ip for five days. Ozone group was administered 1 mg/kg ozone ip for five days. Ischemia Reperfusion (IR group underwent superior mesenteric artery occlusion for one hour and then reperfusion for two hours. Ozone + IR group was administered 1 mg/kg ozone ip for five days and at sixth day IR model was applied. Rats were anesthetized with ketamine∖xyzlazine and their intracardiac blood was drawn completely and they were sacrificed. Intestinal tissue samples were examined under light microscope. Levels of superoxide dismutase (SOD, catalase (CAT, glutathioneperoxidase (GSH-Px, malondyaldehide (MDA, and protein carbonyl (PCO were analyzed in tissue samples. Total oxidant status (TOS, and total antioxidant capacity (TAC were analyzed in blood samples. Data were evaluated statistically by Kruskal Wallis test. Results. In the ozone administered group, degree of intestinal injury was not different from the control group. IR caused an increase in intestinal injury score. The intestinal epithelium maintained its integrity and decrease in intestinal injury score was detected in Ozone + IR group. SOD, GSH-Px, and CAT values were high in ozone group and low in IR. TOS parameter was highest in the IR group and the TAC parameter was highest in the ozone group and lowest in the IR group. Conclusion. In the present study, IR model caused an increase in intestinal injury.In the present study, ozone administration had an effect improving IR associated tissue injury. In the present study, ozone therapy

  10. Surgical treatment of radiation induced injuries of the intestine

    Energy Technology Data Exchange (ETDEWEB)

    Schmitt, E.H.; Symmonds, R.E.

    1981-12-01

    In the patient who has received high dose irradiation of the pelvis and abdomen, all abdominopelvic operations should be avoided, unless it is absolutely essential. Persisting obstruction, hemorrhage, intestinal perforation with peritonitis and with abscess and fistula formation are valid indications for surgical intervention. Ninety-three patients have been operated upon for these complications after irradiation. Some anastomotic dehiscence occurred in ten patients. Six operative deaths occurred. Of the 93 patients, 65 were managed by means of complete resection of the involved segment of intestine, followed by restoration of intestinal continuity by means of an end-to-end anastomosis. This is the treatment of choice when the involved area can be safely resected. In the absence of actual intestinal necrosis and when segments of strictured small intestine are adherent deep in the pelvis, and intestinal bypass procedure may represent the treatment of choice. This was accomplished in 20 patients, two of whom eventually required a second operation for resection of the bypassed segment of intestine.

  11. Surgical treatment of radiation induced injuries of the intestine

    International Nuclear Information System (INIS)

    Schmitt, E.H.; Symmonds, R.E.

    1981-01-01

    In the patient who has received high dose irradiation of the pelvis and abdomen, all abdominopelvic operations should be avoided, unless it is absolutely essential. Persisting obstruction, hemorrhage, intestinal perforation with peritonitis and with abscess and fistula formation are valid indications for surgical intervention. Ninety-three patients have been operated upon for these complications after irradiation. Some anastomotic dehiscence occurred in ten patients. Six operative deaths occurred. Of the 93 patients, 65 were managed by means of complete resection of the involved segment of intestine, followed by restoration of intestinal continuity by means of an end-to-end anastomosis. This is the treatment of choice when the involved area can be safely resected. In the absence of actual intestinal necrosis and when segments of strictured small intestine are adherent deep in the pelvis, and intestinal bypass procedure may represent the treatment of choice. This was accomplished in 20 patients, two of whom eventually required a second operation for resection of the bypassed segment of intestine

  12. 241Am induced thyroid lesions in the beagle: interim observations

    International Nuclear Information System (INIS)

    Taylor, G.N.; Zizumbo, I.; Angus, W.; Jones, A.; Elliot, D.

    1976-01-01

    Injected doses of 2.88, 0.91 or 0.296 μCi 241 Am/kg in young adult beagles produced morphological changes in the thyroid gland and produce lower concentrations of thyroxin in the sera. Interstitial fibrosis without functional impairment was induced by the 0.099 μCi 241 Am/kg dose level. Clinical symptoms of hypothyroidism were not observed, even in those dogs with the most extreme thyroid lesions. The changes were characterized by a decrease in thyroid weight, interfollicular fibrosis, loss of colloid, loss of follicular epithelium, and hypertrophy and hyperplasia of the residual epithelium. Thus far, thyroid tumors have not been observed, however, a significant percentage of the animals in the lower dose levels are still living

  13. A Case of Lung Lesions Induced by a soccer Ball

    Directory of Open Access Journals (Sweden)

    Masaaki Takemoto

    2013-01-01

    Full Text Available An 18-year-old youth soccer forward received a direct hit from a kicked soccer ball on the anterior right chest when the goal keeper kicked the ball from a distance of 1 meter. Immediately following the hit, the subject experienced dypnea, chest pain and had a cough, with several milliliters of hemoptysis. His symptoms subsided after 20 minutes of rest. However, he still felt mild discomfort and was taken to our department for evaluation. On examination, all vital signs were normal. A computed tomography scan of the chest was obtained, and revealed a small area of opacification in the right lung field suggesting a pulmonary contusion or traumatic lung edema. Ten days after the initial injury, he was cleared for full participation. We herein reported the first case of a lung lesion induced by a soccer ball. Conservative treatment resulted in a favorable outcome.

  14. Precision-cut intestinal slices as an in vitro model to predict NSAID induced intestinal toxicity

    NARCIS (Netherlands)

    Niu, Xiaoyu; van der Bijl, Henk; Groothuis, Geny; de Graaf, Inge

    2013-01-01

    Non-steroidal anti-inflammatory drugs (NSAIDs) are associated with high prevalence of gastro-intestinal side-effects. In vivo studies suggest that uncoupling of oxidative phosphorylation is an important cause of the toxicity and that the toxicity is aggravated by enterohepatic circulation.

  15. Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats

    Directory of Open Access Journals (Sweden)

    Pedro M. G. Soares

    2011-03-01

    Full Text Available CONTEXT: Methotrexate and other anticancer agents can induce intestinal mucositis, which is one of the most common limiting factor that prevent further dose escalation of the methotrexate. OBJECTIVES: To evaluate the gastric emptying and gastrointestinal transit of liquids in methotrexate-induced intestinal mucositis. METHODS: Wistar rats received methotrexate (2.5 mg/kg/day for 3 days, subcutaneously or saline. After 1, 3 and 7 days, sections of duodenum, jejunum and ileum were removed for assessment of epithelial damage and myeloperoxidase activity (biochemical marker of granulocyte infiltration. Others rats were pre-treated with methotrexate or saline, gavage-fed after 3 or 7 days with a standard test liquid meal, and sacrificed 10, 20 or 30-min later. Gastric and small intestine dye recoveries were measured by spectrophotometry. RESULTS: After 3 days of methotrexate, there was an epithelial intestinal damage in all segments, with myeloperoxidase activity increase in both in duodenum and ileum. Seven days after methotrexate, we observed a complete reversion of this intestinal damage. There was an increase in gastric dye recoveries after 10, 20, and 30-min post-prandial intervals after 3 days, but not after 7 days, of methotrexate. Intestine dye recoveries were decreased in the first and second segments at 10 min, in the third at 20 min, and in the second and third at 30 min, only after 3 days of methotrexate treatment. CONCLUSION: Methotrexate-induced intestinal mucositis delays gastric emptying and gastrointestinal transit of liquids in awake rats.

  16. Tanshinone IIA Sodium Sulfonate Attenuates LPS-Induced Intestinal Injury in Mice

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    Xin-Jing Yang

    2018-01-01

    Full Text Available Background. Tanshinone IIA sodium sulfonate (TSS is known to possess anti-inflammatory effects and has exhibited protective effects in various inflammatory conditions; however, its role in lipopolysaccharide- (LPS- induced intestinal injury is still unknown. Objective. The present study is designed to explore the role and possible mechanism of TSS in LPS-induced intestinal injury. Methods. Male C57BL/6J mice, challenged with intraperitoneal LPS injection, were treated with or without TSS 0.5 h prior to LPS exposure. At 1, 6, and 12 h after LPS injection, mice were sacrificed, and the small intestine was excised. The intestinal tissue injury was analyzed by HE staining. Inflammatory factors (TNF-α, IL-1β, and IL-6 in the intestinal tissue were examined by ELISA and RT-PCR. In addition, expressions of autophagy markers (microtubule-associated light chain 3 (LC3 and Beclin-1 were detected by western blot and RT-PCR. A number of autophagosomes were also observed under electron microscopy. Results. TSS treatment significantly attenuated small intestinal epithelium injury induced by LPS. LPS-induced release of inflammatory mediators, including TNF-α, IL-1β, and IL-6, were markedly inhibited by TSS. Furthermore, TSS treatment could effectively upregulate LPS-induced decrease of autophagy levels, as evidenced by the increased expression of LC3 and Beclin-1, and more autophagosomes. Conclusion. The protective effect of TSS on LPS-induced small intestinal injury may be attributed to the inhibition of inflammatory factors and promotion of autophagy levels. The present study may provide novel insight into the molecular mechanisms of TSS on the treatment of intestinal injury.

  17. Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

    Energy Technology Data Exchange (ETDEWEB)

    Tang, J.; Jiang, Y. [Southern Medical University, Nanfang Hospital, Department of Anesthesia, Guangzhou, China, Department of Anesthesia, Nanfang Hospital, Southern Medical University, Guangzhou (China); Tang, Y.; Chen, B. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China); Sun, X. [Laboratory of Traditional Chinese Medicine Syndrome, School of Traditional Chinese Medicine, Southern Medical University, Guangzhou (China); Su, L.; Liu, Z. [Guangzhou General Hospital of Guangzhou Military Command, Department of Intensive Care Unit, Guangzhou, China, Department of Intensive Care Unit, Guangzhou General Hospital of Guangzhou Military Command, Guangzhou (China)

    2013-06-25

    Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries.

  18. Effects of propofol on damage of rat intestinal epithelial cells induced by heat stress and lipopolysaccharides

    International Nuclear Information System (INIS)

    Tang, J.; Jiang, Y.; Tang, Y.; Chen, B.; Sun, X.; Su, L.; Liu, Z.

    2013-01-01

    Gut-derived endotoxin and pathogenic bacteria have been proposed as important causative factors of morbidity and death during heat stroke. However, it is still unclear what kind of damage is induced by heat stress. In this study, the rat intestinal epithelial cell line (IEC-6) was treated with heat stress or a combination of heat stress and lipopolysaccharide (LPS). In addition, propofol, which plays an important role in anti-inflammation and organ protection, was applied to study its effects on cellular viability and apoptosis. Heat stress, LPS, or heat stress combined with LPS stimulation can all cause intestinal epithelial cell damage, including early apoptosis and subsequent necrosis. However, propofol can alleviate injuries caused by heat stress, LPS, or the combination of heat stress and LPS. Interestingly, propofol can only mitigate LPS-induced intestinal epithelial cell apoptosis, and has no protective role in heat-stress-induced apoptosis. This study developed a model that can mimic the intestinal heat stress environment. It demonstrates the effects on intestinal epithelial cell damage, and indicated that propofol could be used as a therapeutic drug for the treatment of heat-stress-induced intestinal injuries

  19. Mechanisms of methicillin-resistant Staphylococcus aureus pneumonia-induced intestinal epithelial apoptosis.

    Science.gov (United States)

    Perrone, Erin E; Jung, Enjae; Breed, Elise; Dominguez, Jessica A; Liang, Zhe; Clark, Andrew T; Dunne, W Michael; Burd, Eileen M; Coopersmith, Craig M

    2012-07-01

    Methicillin-resistant Staphylococcus aureus (MRSA) pneumonia-induced sepsis is a common cause of morbidity in the intensive care unit. Although pneumonia is initiated in the lungs, extrapulmonary manifestations occur commonly. In light of the key role the intestine plays in the pathophysiology of sepsis, we sought to determine whether MRSA pneumonia induces intestinal injury. FVB/N mice were subjected to MRSA or sham pneumonia and killed 24 h later. Septic animals had a marked increase in intestinal epithelial apoptosis by both hematoxylin-eosin and active caspase 3 staining. Methicillin-resistant S. aureus-induced intestinal apoptosis was associated with an increase in the expression of the proapoptotic proteins Bid and Bax and the antiapoptotic protein Bcl-xL in the mitochondrial pathway. In the receptor-mediated pathway, MRSA pneumonia induced an increase in Fas ligand but decreased protein levels of Fas, FADD, pFADD, TNF-R1, and TRADD. To assess the functional significance of these changes, MRSA pneumonia was induced in mice with genetic manipulations in proteins in either the mitochondrial or receptor-mediated pathways. Both Bid-/- mice and animals with intestine-specific overexpression of Bcl-2 had decreased intestinal apoptosis compared with wild-type animals. In contrast, Fas ligand-/- mice had no alterations in apoptosis. To determine if these findings were organism-specific, similar experiments were performed in mice subjected to Pseudomonas aeruginosa pneumonia. Pseudomonas aeruginosa induced gut apoptosis, but unlike MRSA, this was associated with increased Bcl-2 and TNF-R1 and decreased Fas. Methicillin-resistant S. aureus pneumonia thus induces organism-specific changes in intestinal apoptosis via changes in both the mitochondrial and receptor-mediated pathways, although the former may be more functionally significant.

  20. Rebamipide suppresses diclofenac-induced intestinal permeability via mitochondrial protection in mice.

    Science.gov (United States)

    Diao, Lei; Mei, Qiao; Xu, Jian-Ming; Liu, Xiao-Chang; Hu, Jing; Jin, Juan; Yao, Qiang; Chen, Mo-Li

    2012-03-14

    To investigate the protective effect and mechanism of rebamipide on small intestinal permeability induced by diclofenac in mice. Diclofenac (2.5 mg/kg) was administered once daily for 3 d orally. A control group received the vehicle by gavage. Rebamipide (100 mg/kg, 200 mg/kg, 400 mg/kg) was administered intragastrically once a day for 3 d 4 h after diclofenac administration. Intestinal permeability was evaluated by Evans blue and the FITC-dextran method. The ultrastructure of the mucosal barrier was evaluated by transmission electron microscopy (TEM). Mitochondrial function including mitochondrial swelling, mitochondrial membrane potential, mitochondrial nicotinamide adenine dinucleotide-reduced (NADH) levels, succinate dehydrogenase (SDH) and ATPase activities were measured. Small intestinal mucosa was collected for assessment of malondialdehyde (MDA) content and myeloperoxidase (MPO) activity. Compared with the control group, intestinal permeability was significantly increased in the diclofenac group, which was accompanied by broken tight junctions, and significant increases in MDA content and MPO activity. Rebamipide significantly reduced intestinal permeability, improved inter-cellular tight junctions, and was associated with decreases in intestinal MDA content and MPO activity. At the mitochondrial level, rebamipide increased SDH and ATPase activities, NADH level and decreased mitochondrial swelling. Increased intestinal permeability induced by diclofenac can be attenuated by rebamipide, which partially contributed to the protection of mitochondrial function.

  1. Tumor Necrosis Factor Induces Developmental Stage-Dependent Structural Changes in the Immature Small Intestine

    Directory of Open Access Journals (Sweden)

    Kathryn S. Brown

    2014-01-01

    Full Text Available Background. Premature infants are commonly subject to intestinal inflammation. Since the human small intestine does not reach maturity until term gestation, premature infants have a unique challenge, as either acute or chronic inflammation may alter the normal development of the intestinal tract. Tumor necrosis factor (TNF has been shown to acutely alter goblet cell numbers and villus length in adult mice. In this study we tested the effects of TNF on villus architecture and epithelial cells at different stages of development of the immature small intestine. Methods. To examine the effects of TNF-induced inflammation, we injected acute, brief, or chronic exposures of TNF in neonatal and juvenile mice. Results. TNF induced significant villus blunting through a TNF receptor-1 (TNFR1 mediated mechanism, leading to loss of villus area. This response to TNFR1 signaling was altered during intestinal development, despite constant TNFR1 protein expression. Acute TNF-mediated signaling also significantly decreased Paneth cells. Conclusions. Taken together, the morphologic changes caused by TNF provide insight as to the effects of inflammation on the developing intestinal tract. Additionally, they suggest a mechanism which, coupled with an immature immune system, may help to explain the unique susceptibility of the immature intestine to inflammatory diseases such as NEC.

  2. Protective effect of superoxide dismutase in radiation-induced intestinal inflammation

    International Nuclear Information System (INIS)

    Molla, Meritxell; Gironella, Meritxell; Salas, Antonio; Closa, Daniel; Biete, Albert; Gimeno, Mercedes; Coronel, Pilar; Pique, Josep M.; Panes, Julian

    2005-01-01

    Purpose: To analyze the therapeutic value of Cu/Zn-superoxide dismutase (SOD1) supplementation in an experimental model of radiation-induced intestinal inflammation and explore its mechanistic effects. Methods and materials: Mice were subjected to abdominal irradiation with 10 Gy or sham irradiation and studied 24 or 72 hours after radiation. Groups of mice were treated with 0.1, 4, or 6 mg/kg/day of SOD1 or vehicle. Leukocyte-endothelial cell interactions in intestinal venules were assessed by intravital microscopy. Endothelial intercellular adhesion molecule-1 (ICAM-1) expression was determined with radiolabeled antibodies. Effects of SOD1 on histologic damage and levels of lipid hydroperoxides were also measured. Results: A significant increase in the flux of rolling leukocytes and number of firmly adherent leukocytes in intestinal venules was observed at 24 and 72 hours after irradiation. Treatment with SOD1 had no effect on leukocyte rolling but significantly and dose-dependently decreased firm leukocyte adhesion to intestinal venules. Treatment with SOD1 at doses that reduced leukocyte recruitment abrogated the increase in hydroperoxides in intestinal tissue and ICAM-1 upregulation in intestinal endothelial cells. The inflammatory score, but not a combined histology damage score, was also significantly reduced by SOD1. Conclusions: Treatment with SOD1 decreases oxidative stress and adhesion molecule upregulation in response to abdominal irradiation. This is associated with an attenuation of the radiation-induced intestinal inflammatory response

  3. Diacylglycerol kinase regulation of protein kinase D during oxidative stress-induced intestinal cell injury

    International Nuclear Information System (INIS)

    Song Jun; Li Jing; Mourot, Joshua M.; Mark Evers, B.; Chung, Dai H.

    2008-01-01

    We recently demonstrated that protein kinase D (PKD) exerts a protective function during oxidative stress-induced intestinal epithelial cell injury; however, the exact role of DAG kinase (DGK)ζ, an isoform expressed in intestine, during this process is unknown. We sought to determine the role of DGK during oxidative stress-induced intestinal cell injury and whether DGK acts as an upstream regulator of PKD. Inhibition of DGK with R59022 compound or DGKζ siRNA transfection decreased H 2 O 2 -induced RIE-1 cell apoptosis as measured by DNA fragmentation and increased PKD phosphorylation. Overexpression of kinase-dead DGKζ also significantly increased PKD phosphorylation. Additionally, endogenous nuclear DGKζ rapidly translocated to the cytoplasm following H 2 O 2 treatment. Our findings demonstrate that DGK is involved in the regulation of oxidative stress-induced intestinal cell injury. PKD activation is induced by DGKζ, suggesting DGK is an upstream regulator of oxidative stress-induced activation of the PKD signaling pathway in intestinal epithelial cells

  4. Effects of growth hormone plus a hyperproteic diet on methotrexate-induced injury in rat intestines.

    Science.gov (United States)

    Ortega, M; Gomez-de-Segura, I A; Vázquez, I; López, J M; de Guevara, C L; De-Miguel, E

    2001-01-01

    The aim of this study was to determine whether growth hormone treatment reduces injury to the intestinal mucosa induced by methotrexate (MTX). Wistar rats with intestinal injury induced by methotrexate were treated with daily growth hormone, beginning 3 days before MTX treatment until 3 or 4 days after MTX administration. The rats were killed at 3 or 7 days post-MTX administration. The rats were fed with either a normoproteic diet or a hyperproteic diet. Body weight, mortality, bacterial translocation, intestinal morphometry, proliferation and apoptosis and blood somatostatin and IGF-1 were determined. Combined administration of growth hormone and a hyperproteic diet reduces MTX-induced mortality. This effect was accompanied by increased cell proliferation and decreased apoptosis within the crypt. Morphometric data showed complete recovery of the mucosa by day 7 post-MTX administration. These results indicate a synergistic protective action of growth hormone combined with a hyperproteic diet to MTX-induced injury.

  5. Soluble Dietary Fibers Can Protect the Small Intestinal Mucosa Without Affecting the Anti-inflammatory Effect of Indomethacin in Adjuvant-Induced Arthritis Rats.

    Science.gov (United States)

    Satoh, Hiroshi; Matsumoto, Hiroki; Hirakawa, Tomoe; Wada, Naoki

    2016-01-01

    How to prevent the small intestinal damage induced by NSAIDs is an urgent issue to be resolved. In the present study, we examined the effects of soluble dietary fibers on both anti-inflammatory and ulcerogenic effects of indomethacin in arthritic rats. Male Wistar rats weighing 180-220 g were used. Arthritis was induced by injecting Freund's complete adjuvant (killed M. tuberculosis) into the plantar region of the right hindpaw. The animals were fed a regular powder diet for rats or a diet supplemented with soluble dietary fibers such as pectin or guar gum. Indomethacin was administered once a day for 3 days starting 14 days after the adjuvant injection, when marked arthritis was observed. The volumes of the hindpaw were measured before and after indomethacin treatment to evaluate the effect of indomethacin on edema. The lesions in the small intestine were examined 24 h after the final dosing of indomethacin. Hindpaw volume was increased about 3 times 14 days after injection of the adjuvant. Indomethacin (3-10 mg/kg, p.o.) decreased hindpaw volume dose-dependently, but caused severe lesions in the small intestine at doses of 6 and 10 mg/kg. The addition of pectin (1-10 %) or guar gum (10 %) to the diet markedly decreased the lesion formation without affecting the anti-edema action of indomethacin. The same effects of pectin were observed when indomethacin was administered subcutaneously. It is suggested that soluble dietary fibers can prevent intestinal damage induced by NSAIDs without affecting the anti-inflammatory effect of these agents.

  6. Impact of cavitation on lesion formation induced by high intensity focused ultrasound

    International Nuclear Information System (INIS)

    Fan Pengfei; Jie Yu; Yang Xin; Tu Juan; Guo Xiasheng; Zhang Dong; Huang Pintong

    2017-01-01

    High intensity focused ultrasound (HIFU) has shown a great promise in noninvasive cancer therapy. The impact of acoustic cavitation on the lesion formation induced by HIFU is investigated both experimentally and theoretically in transparent protein-containing gel and ex vivo liver tissue samples. A numerical model that accounts for nonlinear acoustic propagation and heat transfer is used to simulate the lesion formation induced by the thermal effect. The results showed that lesions could be induced in the samples exposed to HIFU with various acoustic pressures and pulse lengths. The measured areas of lesions formed in the lateral direction were comparable to the simulated results, while much larger discrepancy was observed between the experimental and simulated data for the areas of longitudinal lesion cross-section. Meanwhile, a series of stripe-wiped-off B-mode pictures were obtained by using a special imaging processing method so that HIFU-induced cavitation bubble activities could be monitored in real-time and quantitatively analyzed as the functions of acoustic pressure and pulse length. The results indicated that, unlike the lateral area of HIFU-induced lesion that was less affected by the cavitation activity, the longitudinal cross-section of HIFU-induced lesion was significantly influenced by the generation of cavitation bubbles through the temperature elevation resulting from HIFU exposures. Therefore, considering the clinical safety in HIFU treatments, more attention should be paid on the lesion formation in the longitudinal direction to avoid uncontrollable variation resulting from HIFU-induced cavitation activity. (paper)

  7. Titanium dioxide induced inflammation in the small intestine

    Science.gov (United States)

    Nogueira, Carolina Maciel; de Azevedo, Walter Mendes; Dagli, Maria Lucia Zaidan; Toma, Sérgio Hiroshi; Leite, André Zonetti de Arruda; Lordello, Maria Laura; Nishitokukado, Iêda; Ortiz-Agostinho, Carmen Lúcia; Duarte, Maria Irma Seixas; Ferreira, Marcelo Alves; Sipahi, Aytan Miranda

    2012-01-01

    AIM: To investigate the effects of titanium dioxide (TiO2) nanoparticles (NPTiO2) and microparticles (MPTiO2) on the inflammatory response in the small intestine of mice. METHODS: Bl 57/6 male mice received distilled water suspensions containing TiO2 (100 mg/kg body weight) as NPTiO2 (66 nm), or MPTiO2 (260 nm) by gavage for 10 d, once a day; the control group received only distilled water. At the end of the treatment the duodenum, jejunum and ileum were extracted for assessment of cytokines, inflammatory cells and titanium content. The cytokines interleukin (IL)-1b, IL-4, IL-6, IL-8, IL-10, IL-12, IL-13, IL-17, IL-23, tumor necrosis factor-α (TNF-α), intracellular interferon-γ (IFN-γ) and transforming growth factor-β (TGF-β) were evaluated by enzyme-linked immunosorbent assay in segments of jejunum and ileum (mucosa and underlying muscular tissue). CD4+ and CD8+ T cells, natural killer cells, and dendritic cells were evaluated in duodenum, jejunum and ileum samples fixed in 10% formalin by immunohistochemistry. The titanium content was determined by inductively coupled plasma atomic emission spectrometry. RESULTS: We found increased levels of T CD4+ cells (cells/mm2) in duodenum: NP 1240 ± 139.4, MP 1070 ± 154.7 vs 458 ± 50.39 (P < 0.01); jejunum: NP 908.4 ± 130.3, MP 813.8 ± 103.8 vs 526.6 ± 61.43 (P < 0.05); and ileum: NP 818.60 ± 123.0, MP 640.1 ± 32.75 vs 466.9 ± 22.4 (P < 0.05). In comparison to the control group, the groups receiving TiO2 showed a statistically significant increase in the levels of the inflammatory cytokines IL-12, IL-4, IL-23, TNF-α, IFN-γ and TGF-β. The cytokine production was more pronounced in the ileum (mean ± SE): IL-12: NP 33.98 ± 11.76, MP 74.11 ± 25.65 vs 19.06 ± 3.92 (P < 0.05); IL-4: NP 17.36 ± 9.96, MP 22.94 ± 7.47 vs 2.19 ± 0.65 (P < 0.05); IL-23: NP 157.20 ± 75.80, MP 134.50 ± 38.31 vs 22.34 ± 5.81 (P < 0.05); TNFα: NP 3.71 ± 1.33, MP 5.44 ± 1.67 vs 0.99 ± 019 (P < 0.05); IFNγ: NP 15.85 ± 9

  8. Dunnione ameliorates cisplatin-induced small intestinal damage by modulating NAD{sup +} metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Pandit, Arpana; Kim, Hyung-Jin; Oh, Gi-Su; Shen, AiHua; Lee, Su-Bin; Khadka, Dipendra; Lee, SeungHoon [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Shim, Hyeok; Yang, Sei-Hoon; Cho, Eun-Young [Department of Internal Medicine, School of Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwon, Kang-Beom [Department of Oriental Medical Physiology, School of Oriental Medicine, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); Kwak, Tae Hwan [PAEAN Biotechnology, 160 Techno-2 Street, Yuseong-gu, Daejeon 305-500 (Korea, Republic of); Choe, Seong-Kyu; Park, Raekil [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of); So, Hong-Seob, E-mail: jeanso@wku.ac.kr [Center for Metabolic Function Regulation & Department of Microbiology, Wonkwang University, Iksan, Jeonbuk 570-749 (Korea, Republic of)

    2015-11-27

    Although cisplatin is a widely used anticancer drug for the treatment of a variety of tumors, its use is critically limited because of adverse effects such as ototoxicity, nephrotoxicity, neuropathy, and gastrointestinal damage. Cisplatin treatment increases oxidative stress biomarkers in the small intestine, which may induce apoptosis of epithelial cells and thereby elicit damage to the small intestine. Nicotinamide adenine dinucleotide (NAD{sup +}) is a cofactor for various enzymes associated with cellular homeostasis. In the present study, we demonstrated that the hyper-activation of poly(ADP-ribose) polymerase-1 (PARP-1) is closely associated with the depletion of NAD{sup +} in the small intestine after cisplatin treatment, which results in downregulation of sirtuin1 (SIRT1) activity. Furthermore, a decrease in SIRT1 activity was found to play an important role in cisplatin-mediated small intestinal damage through nuclear factor (NF)-κB p65 activation, facilitated by its acetylation increase. However, use of dunnione as a strong substrate for the NADH:quinone oxidoreductase 1 (NQO1) enzyme led to an increase in intracellular NAD{sup +} levels and prevented the cisplatin-induced small intestinal damage correlating with the modulation of PARP-1, SIRT1, and NF-κB. These results suggest that direct modulation of cellular NAD{sup +} levels by pharmacological NQO1 substrates could be a promising therapeutic approach for protecting against cisplatin-induced small intestinal damage. - Highlights: • NAD{sup +} acts as a cofactor for numerous enzymes including Sirtuins and PARP. • Up-regulation of SIRT1 could attenuate the cisplatin-induced intestinal damage. • Modulation of the cellular NAD{sup +} could be a promising therapeutic approach.

  9. Lactobacillus salivarius reverse diabetes-induced intestinal defense impairment in mice through non-defensin protein.

    Science.gov (United States)

    Chung, Pei-Hsuan; Wu, Ying-Ying; Chen, Pei-Hsuan; Fung, Chang-Phone; Hsu, Ching-Mei; Chen, Lee-Wei

    2016-09-01

    Altered intestinal microbiota and subsequent endotoxemia play pathogenic roles in diabetes. We aimed to study the mechanisms of intestinal defense impairment in type 1 diabetes and the effects of Lactobacillus salivarius as well as fructooligosaccharides (FOS) supplementation on diabetes-induced bacterial translocation. Alterations in the enteric microbiome, expression of mucosal antibacterial proteins and bacteria-killing activity of the intestinal mucosa in streptozotocin (STZ)-induced diabetic mice and Ins2(Akita) mice were investigated. The effects of dead L. salivarius (2×10(8)CFU/ml) and FOS (250 mg per day) supplementation for 1 week on endotoxin levels and Klebsiella pneumoniae translocation were also examined. Finally, germ-free mice were cohoused with wild-type or Ins2(Akita) mice for 2 weeks to examine the contribution of microbiota on the antibacterial protein expression. STZ-induced diabetic mice developed intestinal defense impairment as demonstrated by decreased mucosal bacteria-killing activity; reduction of non-defensin family proteins, such as Reg3β, Reg3γ, CRP-ductin and RELMβ, but not the defensin family proteins; and increased bacterial translocation. Intestinal bacteria overgrowth, enteric dysbiosis and increased intestinal bacterial translocation, particularly pathogenic K. pneumoniae in STZ-induced diabetic mice and Ins2(Akita) mice, were noted. Treating diabetic mice with dead L. salivarius or FOS reversed enteric dysbiosis, restored mucosal antibacterial protein and lessened endotoxin levels as well as K. pneumoniae translocation. Moreover, germ-free mice cohoused with wild-type mice demonstrated more intestinal Reg3β and RELMβ expression than those cohoused with Ins2(Akita) mice. These results indicate that hyperglycemia induces enteric dysbiosis, reduction of non-defensin proteins as well as bacteria-killing activity of the intestinal mucosa and intestinal defense impairment. Reversal of enteric dysbiosis with dead L. salivarius or

  10. Spontaneous and x-irradiation induced carcinomas of small intestine in Wistar-Furth rats

    Energy Technology Data Exchange (ETDEWEB)

    Maeura, Y; Kosaki, G; Kitamura, H [Osaka Univ. (Japan). Faculty of Medicine; Nagatomo, T

    1980-04-01

    Spontaneous carcinoma of the small intestine in Wistar-Furth (WF) rats and carcinoma of the small intestine induced by local x-ray irradiation to the abdomen of WF rats without carcinoma were observed, and x-ray sensitivity of the small intestine mucosa was reported. Out of 19 rats with spontaneous carcinoma of the small intestine, 18 also had carcinoma of the colon, and 4 also had gastric cancer. They already had spontaneous carcinoma of the small intestine within 2 weeks after their birth, and the ratio of female and male was 13 : 6. Histological type of this carcinoma in all 19 rats was highly differentiated adenocarcinoma, and small intestine epithelium around carcinoma presented atypical epithelium. As to mice without carcinoma, x-ray, 1,000 R, 1,500 R, and 2,000 R, was irradiated to the abdomen of Sprague-Dawley (SD) and WF rats. In the irradiation with 1,000 R, carcinogenesis was not found in rats of both strains. In the irradiation with 1,500 R, carcinogenesis was hardly found, but in the irradiation with 2,000 R, carcinoma of small intestine occurred in 5 of 17 rats 15 weeks after the irradiation, 9 of 19 rats 25 weeks after the irradiation, and 9 of 14 rats 35 weeks after the irradiation. Histological type of carcinoma in irradiated rats was highly differentiated adenocarcinoma. The incidence of carcinoma in irradiated rats was higher in WF rats than SD rats through the course after the irradiation, which suggested that x-ray sensitivity of WF rats was higher than that of SD rats. Therefore, carcinoma of the small intestine in irradiated mice seemed to be induced by x-ray.

  11. PAI-1-dependent endothelial cell death determines severity of radiation-induced intestinal injury.

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    Rym Abderrahmani

    Full Text Available Normal tissue toxicity still remains a dose-limiting factor in clinical radiation therapy. Recently, plasminogen activator inhibitor type 1 (SERPINE1/PAI-1 was reported as an essential mediator of late radiation-induced intestinal injury. However, it is not clear whether PAI-1 plays a role in acute radiation-induced intestinal damage and we hypothesized that PAI-1 may play a role in the endothelium radiosensitivity. In vivo, in a model of radiation enteropathy in PAI-1 -/- mice, apoptosis of radiosensitive compartments, epithelial and microvascular endothelium was quantified. In vitro, the role of PAI-1 in the radiation-induced endothelial cells (ECs death was investigated. The level of apoptotic ECs is lower in PAI-1 -/- compared with Wt mice after irradiation. This is associated with a conserved microvascular density and consequently with a better mucosal integrity in PAI-1 -/- mice. In vitro, irradiation rapidly stimulates PAI-1 expression in ECs and radiation sensitivity is increased in ECs that stably overexpress PAI-1, whereas PAI-1 knockdown increases EC survival after irradiation. Moreover, ECs prepared from PAI-1 -/- mice are more resistant to radiation-induced cell death than Wt ECs and this is associated with activation of the Akt pathway. This study demonstrates that PAI-1 plays a key role in radiation-induced EC death in the intestine and suggests that this contributes strongly to the progression of radiation-induced intestinal injury.

  12. Effects of experimentally induced intestinal obstruction on the electrolyte profile in dogs

    International Nuclear Information System (INIS)

    Dar, E.M.; Khan, M.A.; Mehmood, A.K.

    2004-01-01

    This study was conducted to quantitatively asses the changes in serum electrolyte profile after experimentally induced upper and lower intestinal obstruction in dogs. Ten dogs of either sex ranging in weight from 20-25 Kg were selected. After thorough physical examination, de-worming and vaccination they were randomly divided into 3 groups. Groups A and B comprised of four animals each while group C had two animals. After preparing the operation site, upper intestinal obstruction was induced in animals of group A and lower intestinal obstruction was induced in all animals of group B through mid line laparotomy under general anesthesia. Animals of group C were kept as control without induction of any obstruction. Proper post-operative care was given to the operated animals. Blood samples were collected from all animals at an interval of 24 hours and evaluated to observe changes in serum sodium, potassium and chloride levels. The results of this study showed marked decline in electrolyte levels in animals of both groups A and B, however this decline was more severe and rapid in group A than group B, while group c acted normally. It can be concluded that upper intestinal obstruction is more fatal in its consequences than lower intestinal obstruction, which is relatively less dangerous in producing its ill effects. (author)

  13. Intestinal upregulation of melanin-concentrating hormone in TNBS-induced enterocolitis in adult zebrafish.

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    Brenda M Geiger

    Full Text Available BACKGROUND: Melanin-concentrating hormone (MCH, an evolutionarily conserved appetite-regulating neuropeptide, has been recently implicated in the pathogenesis of inflammatory bowel disease (IBD. Expression of MCH is upregulated in inflamed intestinal mucosa in humans with colitis and MCH-deficient mice treated with trinitrobenzene-sulfonic acid (TNBS develop an attenuated form of colitis compared to wild type animals. Zebrafish have emerged as a new animal model of IBD, although the majority of the reported studies concern zebrafish larvae. Regulation MCH expression in the adult zebrafish intestine remains unknown. METHODS: In the present study we induced enterocolitis in adult zebrafish by intrarectal administration of TNBS. Follow-up included survival analysis, histological assessment of changes in intestinal architecture, and assessment of intestinal infiltration by myeloperoxidase positive cells and cytokine transcript levels. RESULTS: Treatment with TNBS dose-dependently reduced fish survival. This response required the presence of an intact microbiome, since fish pre-treated with vancomycin developed less severe enterocolitis. At 6 hours post-challenge, we detected a significant influx of myeloperoxidase positive cells in the intestine and upregulation of both proinflammatory and anti-inflammatory cytokines. Most importantly, and in analogy to human IBD and TNBS-induced mouse experimental colitis, we found increased intestinal expression of MCH and its receptor in TNBS-treated zebrafish. CONCLUSIONS: Taken together these findings not only establish a model of chemically-induced experimental enterocolitis in adult zebrafish, but point to effects of MCH in intestinal inflammation that are conserved across species.

  14. Effects of Berberine Against Radiation-Induced Intestinal Injury in Mice

    International Nuclear Information System (INIS)

    Li Guanghui; Zhang Yaping; Tang Jinliang; Chen Zhengtang; Hu Yide; Wei Hong; Li Dezhi; Hao Ping; Wang Donglin

    2010-01-01

    Purpose: Radiation-induced intestinal injury is a significant clinical problem in patients undergoing abdominal radiotherapy (RT). Berberine has been used as an antimicrobial, anti-inflammatory, and antimotility agent. The present study investigated the protective effect of berberine against radiation-induced intestinal injury. Methods and Materials: The mice were administrated berberine or distilled water. A total of 144 mice underwent 0, 3, 6, 12, or 16 Gy single session whole-abdominal RT and 16 mice underwent 3 Gy/fraction/d for four fractions of fractionated abdominal RT. Tumor necrosis factor-α, interleukin-10, diamine oxidase, intestinal fatty acid-binding protein, malonaldehyde, and apoptosis were assayed in the mice after RT. The body weight and food intake of the mice receiving fractionated RT were recorded. Another 72 mice who had undergone 12, 16, or 20 Gy abdominal RT were monitored for mortality every 12 h. Results: The body weight and food intake of the mice administered with distilled water decreased significantly compared with before RT. After the same dose of abdominal RT, tumor necrosis factor-α, diamine oxidase, intestinal fatty acid-binding protein in plasma and malonalhehyde and apoptosis of the intestine were significantly greater in the control group than in the mice administered berberine (p < .05-.01). In contrast, interleukin-10 in the mice with berberine treatment was significantly greater than in the control group (p < .01). A similar result was found in the fractionated RT experiment and at different points after 16 Gy abdominal RT (p < .05-.01). Berberine treatment significantly delayed the point of death after 20 Gy, but not 16 Gy, abdominal RT (p < .01). Conclusion: Treatment with berberine can delay mortality and attenuated intestinal injury in mice undergoing whole abdominal RT. These findings could provide a useful therapeutic strategy for radiation-induced intestinal injury.

  15. Tolerogenic CX3CR1+ B cells suppress food allergy-induced intestinal inflammation in mice.

    Science.gov (United States)

    Liu, Z Q; Wu, Y; Song, J P; Liu, X; Liu, Z; Zheng, P Y; Yang, P C

    2013-10-01

    B lymphocytes are an important cell population of the immune regulation; their role in the regulation of food allergy has not been fully understood yet. This study aims to investigate the role of a subpopulation of tolerogenic B cells (TolBC) in the generation of regulatory T cells (Treg) and in the suppression of food allergy-induced intestinal inflammation in mice. The intestinal mucosa-derived CD5+ CD19+ CX3CR1+ TolBCs were characterized by flow cytometry; a mouse model of intestinal T helper (Th)2 inflammation was established to assess the immune regulatory role of this subpopulation of TolBCs. A subpopulation of CD5+ CD19+ CX3CR1+ B cells was detected in the mouse intestinal mucosa. The cells also expressed transforming growth factor (TGF)-β and carried integrin alpha v beta 6 (αvβ6). Exposure to recombinant αvβ6 and anti-IgM antibody induced naive B cells to differentiate into the TGF-β-producing TolBCs. Coculturing this subpopulation of TolBCs with Th0 cells generated CD4+ CD25+ Foxp3+ Tregs. Adoptive transfer with the TolBCs markedly suppressed the food allergy-induced intestinal Th2 pattern inflammation in mice. CD5+ CD19+ CX3CR1+ TolBCs are capable of inducing Tregs in the intestine and suppress food allergy-related Th2 pattern inflammation in mice. © 2013 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  16. Partridge embryo pathology in relation to gentamicin-induced lesions

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    Hadi Tavakkoli

    2016-10-01

    Full Text Available Objective: To determine the macroscopic and microscopic lesions of various dosages of gentamicin in the partridge embryo. Methods: Fertile chukar partridge eggs were allocated into four groups. Group 1: salineinjected group whose individuals were administered by sterile physiological saline solution of 0.2 mL/egg inserted into yolk sac. Groups 2, 3 and 4 whose individuals were similarly administered by gentamicin sulfate at a dosage of 80 mg/kg egg-weight once, twice and three times, respectively. Results: Results showed that the embryos were congested and stunted in the gentamicininjected groups. Defects in feet, wings and feather development were accompanied by microscopic lesions in brain, meninges, heart, lungs, liver and kidneys. Histopathological lesions were noticed as edema, undeveloped tissues, necrosis and degeneration in the affected organs. Conclusions: Based on acquired results, it is concluded that gentamicin at above-described dosages causes toxicopathological effects to the partridge embryo in a dose dependent manner.

  17. Localized lesions induced by 137Cs during the Goiania accident

    International Nuclear Information System (INIS)

    Oliveira, A.R.; Brandao-Mello, C.E.; Valverde, N.J.; Farina, R.; Curado, M.P.

    1991-01-01

    A description is given of initial symptoms and clinical observations regarding acute localized radiation lesions in 28 persons exposed to 137Cs during the Goiania radiological accident. Specialized procedures to estimate the extent and gravity of the lesions and establish a therapeutic strategy, as well as to anticipate the prognosis in each case, are briefly discussed. Measures taken for reduction of pain and inflammation are noted, and an explanation is given for difficulties encountered due to adverse working conditions and the serious clinical manifestations presented by various patients concomitantly with their lesions. Also noted is the difficulty in obtaining credible information regarding exposure, such as source-to-object distance, duration of exposure, and source activity, which precluded dosimetry studies in most cases

  18. A Refined Culture System for Human Induced Pluripotent Stem Cell-Derived Intestinal Epithelial Organoids

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    Yu Takahashi

    2018-01-01

    Full Text Available Gut epithelial organoids are routinely used to investigate intestinal biology; however, current culture methods are not amenable to genetic manipulation, and it is difficult to generate sufficient numbers for high-throughput studies. Here, we present an improved culture system of human induced pluripotent stem cell (iPSC-derived intestinal organoids involving four methodological advances. (1 We adopted a lentiviral vector to readily establish and optimize conditioned medium for human intestinal organoid culture. (2 We obtained intestinal organoids from human iPSCs more efficiently by supplementing WNT3A and fibroblast growth factor 2 to induce differentiation into definitive endoderm. (3 Using 2D culture, followed by re-establishment of organoids, we achieved an efficient transduction of exogenous genes in organoids. (4 We investigated suspension organoid culture without scaffolds for easier harvesting and assays. These techniques enable us to develop, maintain, and expand intestinal organoids readily and quickly at low cost, facilitating high-throughput screening of pathogenic factors and candidate treatments for gastrointestinal diseases.

  19. Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

    NARCIS (Netherlands)

    The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; van der Heide, S.; van den Wijngaard, R. M.; de Jonge, W. J.; Boeckxstaens, G. E.

    2008-01-01

    Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

  20. Intestinal handling-induced mast cell activation and inflammation in human postoperative ileus

    NARCIS (Netherlands)

    The, F. O.; Bennink, R. J.; Ankum, W. M.; Buist, M. R.; Busch, O. R. C.; Gouma, D. J.; Van der Heide, S.; van den Wijngaard, R. M.; Boeckxstaens, G. E.; de Jonge, Wouter J.

    Background: Murine postoperative ileus results from intestinal inflammation triggered by manipulation-induced mast cell activation. As its extent depends on the degree of handling and subsequent inflammation, it is hypothesised that the faster recovery after minimal invasive surgery results from

  1. Radiation-induced liver lesions in beagle dogs

    International Nuclear Information System (INIS)

    Hahn, F.F.; Muggenburg, B.A.; Boecker, B.B.

    1994-01-01

    The risk for liver disease from internally deposited beta-emitting radionuclides is unknown because there are no human populations exposed to hepatotropic beta-emitting radionuclides available for study. In this report, we discuss the hepatic lesion in dogs exposed to a beta-emitting radionuclide, 144 CeCl 3 , and held for their life spans

  2. Treatment and prophylaxis with sucralfate ameliorates hypoxia/reoxygenation-induced intestinal injury in pup rats.

    Science.gov (United States)

    Sencan, Arzu Bostanci; Sencan, Aydin; Aktas, Safiye; Habif, Sara; Kabaroglu, Ceyda; Parildar, Zuhal; Karaca, Irfan

    2005-04-01

    Sucralfate is widely used as a cytoprotective agent in patients with peptic ulcer and other intestinal mucosal injury. The aim of this study is to investigate whether sucralfate has any effect on the prevention and treatment of hypoxia/reoxygenation-induced intestinal injury. Four groups of 10 1-day-old rat pups were studied. Hypoxia/reoxygenation (H/O)-induced intestinal injury was created. Group 1 was subjected to H/O just after birth and sacrificed at the end of the third day (Treatment Control). Group 2 was subjected to H/O just after birth and treated with sucralfate for 3 days. They were sacrificed at the end of the third day (Treatment). Group 3 was subjected to H/O on the third day after birth and then sacrificed (Prophylaxis Control). Group 4 was treated with sucralfate for the first 3 days, then H/O was created. Just after H/O, the pups were sacrificed (Prophylaxis). The intestinal tissues were harvested for histopathological investigation. Malondialdehyde (MDA) levels in the intestinal tissues were determined. The mucosal injury grades of the treatment and prophylaxis groups were significantly lower than those of control groups (p<0.05). The mean MDA level in the treatment and prophylaxis groups were 0.42+/-0.17 and 0.21+/-0.23 nmol/mg respectively. The MDA levels of both groups were significantly lower than in the control groups (p<0.05). The present study shows that sucralfate has beneficial effects in an experimental model of hypoxia/reoxygenation-induced intestinal injury.

  3. Lesion bacterial communities in American lobsters with diet-induced shell disease.

    Science.gov (United States)

    Quinn, Robert A; Metzler, Anita; Tlusty, Michael; Smolowitz, Roxanna M; Leberg, Paul; Chistoserdov, Andrei Y

    2012-04-26

    In southern New England, USA, shell disease affects the profitability of the American lobster Homarus americanus fishery. In laboratory trials using juvenile lobsters, exclusive feeding of herring Clupea harengus induces shell disease typified initially by small melanized spots that progress into distinct lesions. Amongst a cohabitated, but segregated, cohort of 11 juvenile lobsters fed exclusively herring, bacterial communities colonizing spots and lesions were investigated by denaturing gradient gel electrophoresis of 16S rDNA amplified using 1 group-specific and 2 universal primer sets. The Bacteroidetes and Proteobacteria predominated in both spots and lesions and included members of the orders Flavobacteriales (Bacteriodetes), Rhodobacterales, Rhodospirillales and Rhizobiales (Alphaproteobacteria), Xanthomonadales (Gammaproteobacteria) and unclassified Gammaproteobacteria. Bacterial communities in spot lesions displayed more diversity than communities with larger (older) lesions, indicating that the lesion communities stabilize over time. At least 8 bacterial types persisted as lesions developed from spots. Aquimarina 'homaria', a species commonly cultured from lesions present on wild lobsters with epizootic shell disease, was found ubiquitously in spots and lesions, as was the 'Candidatus Kopriimonas aquarianus', implicating putative roles of these species in diet-induced shell disease of captive lobsters.

  4. Does sucralfate prevent apoptosis occurring in the ischemia/reperfusion-induced intestinal injury?

    Science.gov (United States)

    Sencan, A; Yilmaz, O; Ozer, E; Günşar, C; Genç, K; Ulukuş, C; Taneli, C; Mir, E

    2003-08-01

    We have shown in a previous study that sucralfate is beneficial in the prophylaxis and treatment of hypoxia/reoxygenation-induced intestinal injury. The aim of this study is to investigate whether sucralfate has any effect on the prevention of apoptosis in the ischemia/reperfusion (I/R)-induced intestinal injury. Rats were randomized into three groups. Group 1 and 2 were subjected to I/R. Group 1 (treatment group) received sucralfate while group 2 (treatment control group) did not. Group 3 served as a normal control group (sham group). The terminal ileum was harvested for histopathologic investigation by light microscopy. The presence of apoptotic enterocytes (DNA fragmentation in cell nuclei) was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end-labeling (TUNEL) reaction. In treatment control group, 3 of 7 rats had severe inflammation. None of the sucralfate-treated rats showed severe inflammation, 6 of them only showed mild inflammatory changes (p < 0.05). The apoptotic percentage was found to be 37.1 +/- 9.4 in the sucralfate-treated group (group 1), whereas it was 45.4 +/- 3.9 in the untreated group (group 2) (p < 0.05). The sham group had a completely normal intestinal architecture. The present study shows that 1) the experimental model of I/R-induced intestinal injury induces enterocyte apoptosis; 2) sucralfate decreases enterocyte apoptosis in the experimental model of I/R-induced intestinal injury which may play a key role in the pathophysiological events leading to failure of the intrinsic gut barrier defense mechanisms.

  5. Somatostatin does not attenuate intestinal injury in dextran sodium sulphate-induced subacute colitis

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    J. D. van Bergeijk

    1998-01-01

    Full Text Available From several in vitro and in vivo studies involvement of som atostatin (SMS in intestinal inflammation emerge. Acute colitis induced in rats is attenuated by the long-acting SMS analogue octreotide. We studied the potential beneficial effect of SMS on non-acute experimental colitis. BALB/c mice received either saline, SMS-14 (36 or 120 μg daily or octreotide (3 μg daily subcutaneously delivered by implant osmotic pumps. A non-acute colitis was induced by administration of dextran sodium sulphate (DSS 10% in drinking water during 7 days. DSS evoked a mild, superficial pancolitis, most characterized by mucosal ulceration and submucosal influx of neutrophils. Neither SMS-14 nor octreotide reduced mucosal inflammatory score or macroscopical disease activity, although reduction of intestinal levels of interleukin1 β (IL-1 β, IL-6 and IL-10 during DSS was augmented both by SMS and octreotide. A slight increase of neutrophil influx was seen during SMS administration in animals not exposed to DSS. In conclusion, SMS or its long-acting analogue did not reduce intestinal inflammation in non-acute DSS-induced colitis. According to the cytokine profile observed, SMS-14 and octreotide further diminished the reduction of intestinal macrophage and Th2 lymphocyte activity.

  6. Lactobacillus GG and tributyrin supplementation reduce antibiotic-induced intestinal injury.

    Science.gov (United States)

    Cresci, Gail; Nagy, Laura E; Ganapathy, Vadivel

    2013-11-01

    Antibiotic therapy negatively alters the gut microbiota. Lactobacillus GG (LGG) decreases antibiotic-associated diarrhea (AAD) symptoms, but the mechanisms are unknown. Butyrate has beneficial effects on gut health. Altered intestinal gene expression occurs in the absence of gut microbiota. We hypothesized that antibiotic-induced changes in gut microbiota reduce butyrate production, varying genes involved with gut barrier integrity and water and electrolyte absorption, lending to AAD, and that simultaneous supplementation with LGG and/or tributyrin would prevent these changes. C57BL/6 mice aged 6-8 weeks received a chow diet while divided into 8 treatment groups (± saline, ± LGG, ± tributyrin, or both). Mice received treatments orally for 7 days with ± broad-spectrum antibiotics. Water intake was recorded daily and body weight was measured. Intestine tissue samples were obtained and analyzed for expression of genes and proteins involved with water and electrolyte absorption, butyrate transport, and gut integrity via polymerase chain reaction and immunohistochemistry. Antibiotics decreased messenger RNA (mRNA) expression (butyrate transporter and receptor, Na(+)/H(+) exchanger, Cl(-)/HCO3 (-), and a water channel) and protein expression (butyrate transporter, Na(+)/H(+) exchanger, and tight junction proteins) in the intestinal tract. LGG and/or tributyrin supplementation maintained intestinal mRNA expression to that of the control animals, and tributyrin maintained intestinal protein intensity expression to that of control animals. Broad-spectrum antibiotics decrease expression of anion exchangers, butyrate transporter and receptor, and tight junction proteins in mouse intestine. Simultaneous oral supplementation with LGG and/or tributyrin minimizes these losses. Optimizing intestinal health with LGG and/or tributyrin may offer a preventative therapy for AAD.

  7. Saccharomyces cerevisiae Boulardii Reduces the Deoxynivalenol-Induced Alteration of the Intestinal Transcriptome

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    Imourana Alassane-Kpembi

    2018-05-01

    Full Text Available Type B trichothecene mycotoxin deoxynivalenol (DON is one of the most frequently occurring food contaminants. By inducing trans-activation of a number of pro-inflammatory cytokines and increasing the stability of their mRNA, trichothecene can impair intestinal health. Several yeast products, especially Saccharomyces cerevisiae, have the potential for improving the enteric health of piglets, but little is known about the mechanisms by which the administration of yeast counteracts the DON-induced intestinal alterations. Using a pig jejunum explant model, a whole-transcriptome analysis was performed to decipher the early response of the small intestine to the deleterious effects of DON after administration of S. cerevisiae boulardii strain CNCM I-1079. Compared to the control condition, no differentially expressed gene (DE was observed after treatment by yeast only. By contrast, 3619 probes—corresponding to 2771 genes—were differentially expressed following exposure to DON, and 32 signaling pathways were identified from the IPA software functional analysis of the set of DE genes. When the intestinal explants were treated with S. cerevisiae boulardii prior to DON exposure, the number of DE genes decreased by half (1718 probes corresponding to 1384 genes. Prototypical inflammation signaling pathways triggered by DON, including NF-κB and p38 MAPK, were reversed, although the yeast demonstrated limited efficacy toward some other pathways. S. cerevisiae boulardii also restored the lipid metabolism signaling pathway, and reversed the down-regulation of the antioxidant action of vitamin C signaling pathway. The latter effect could reduce the burden of DON-induced oxidative stress. Altogether, the results show that S. cerevisiae boulardii reduces the DON-induced alteration of intestinal transcriptome, and point to new mechanisms for the healing of tissue injury by yeast.

  8. Saccharomyces cerevisiae Boulardii Reduces the Deoxynivalenol-Induced Alteration of the Intestinal Transcriptome.

    Science.gov (United States)

    Alassane-Kpembi, Imourana; Pinton, Philippe; Hupé, Jean-François; Neves, Manon; Lippi, Yannick; Combes, Sylvie; Castex, Mathieu; Oswald, Isabelle P

    2018-05-15

    Type B trichothecene mycotoxin deoxynivalenol (DON) is one of the most frequently occurring food contaminants. By inducing trans-activation of a number of pro-inflammatory cytokines and increasing the stability of their mRNA, trichothecene can impair intestinal health. Several yeast products, especially Saccharomyces cerevisiae , have the potential for improving the enteric health of piglets, but little is known about the mechanisms by which the administration of yeast counteracts the DON-induced intestinal alterations. Using a pig jejunum explant model, a whole-transcriptome analysis was performed to decipher the early response of the small intestine to the deleterious effects of DON after administration of S. cerevisiae boulardii strain CNCM I-1079. Compared to the control condition, no differentially expressed gene (DE) was observed after treatment by yeast only. By contrast, 3619 probes-corresponding to 2771 genes-were differentially expressed following exposure to DON, and 32 signaling pathways were identified from the IPA software functional analysis of the set of DE genes. When the intestinal explants were treated with S. cerevisiae boulardii prior to DON exposure, the number of DE genes decreased by half (1718 probes corresponding to 1384 genes). Prototypical inflammation signaling pathways triggered by DON, including NF-κB and p38 MAPK, were reversed, although the yeast demonstrated limited efficacy toward some other pathways. S. cerevisiae boulardii also restored the lipid metabolism signaling pathway, and reversed the down-regulation of the antioxidant action of vitamin C signaling pathway. The latter effect could reduce the burden of DON-induced oxidative stress. Altogether, the results show that S. cerevisiae boulardii reduces the DON-induced alteration of intestinal transcriptome, and point to new mechanisms for the healing of tissue injury by yeast.

  9. Intestinal helminths induce haematological changes in dogs from Jabalpur, India.

    Science.gov (United States)

    Qadir, S; Dixit, A K; Dixit, P; Sharma, R L

    2011-12-01

    The effect of canine intestinal helminths on the haematological profile of 200 dogs, of both sexes and variable age, visiting university veterinary clinics for routine examination was investigated. The dogs were assigned to parasitized (n = 39) and non-parasitized (n = 161) groups of animals. Coprological examination revealed a 19.5% prevalence of different species of the helminths. Of these animals, 10.25% had mixed infections with Ancylostoma caninum, Toxascaris spp. and Dipylidium caninum. The intensity of A. caninum infection was the highest, with mean egg counts of 951.43 (standard error 88.66), followed by Toxascaris 283.33 (standard error 116.81) and D. caninum. The parasitized animals had significantly lower levels of haemoglobin, packed cell volume and total erythrocyte counts than non-parasitized animals (P < 0.01). Values of other parameters, except for lymphocytes and eosinophils, were not different between the two groups. Analyses of the haematological profile revealed normocytic hypochromic anaemia in the parasitized group of animals.

  10. Attenuative effects of G-CSF in radiation induced intestinal injury

    International Nuclear Information System (INIS)

    Kim, Joong Sun; Gong, Eun Ji; Kim, Sung Dae; Heo, Kyu; Ryoo, Seung Bum; Yang, Kwang Mo

    2011-01-01

    Granulocyte colony stimulating factor (G-CSF) has been reported to protect from radiationinduced myelosuppression. Growing evidence suggests that G-CSF also has many important non-hematopoietic functions in other tissues, including the intestine (Kim et al., 2010; Kim et al., 2011). However, little is known about the influence of G-CSF on intestinal injury. Examination 12 hours after radiation (5 Gy) revealed that the G-CSF treated mice were significantly protected from apoptosis of jejunal crypt, compared with radiation controls. G-CSF treatment attenuated intestinal morphological changes such as decreased survival crypt, the number of villi, villous shortening, crypt depth and length of basal lamina of 10 enterocytes compared with the radiation control 3.5 days after radiation (10 Gy). G-CSF attenuated the change of peripheral blood from radiation-induced myelosuppression and displayed attenuation of mortality in lethally-irradiated (10 Gy) mice. The present results support the suggestion that G-CSF administrated prior to radiation plays an important role in the survival of irradiated mice, possibly due to the protection of hematopoietic cells and intestinal stem cells against radiation. The results indicate that G-CSF protects from radiation-mediated intestinal damage and from hematopoietic injury. G-CSF treatment may be useful clinically in the prevention of injury following radiation.

  11. Inducing effect of clofibric acid on stearoyl-CoA desaturase in intestinal mucosa of rats.

    Science.gov (United States)

    Yamazaki, Tohru; Kadokura, Makiko; Mutoh, Yuki; Sakamoto, Takeshi; Okazaki, Mari; Mitsumoto, Atsushi; Kawashima, Yoichi; Kudo, Naomi

    2014-12-01

    Fibrates have been reported to elevate the hepatic proportion of oleic acid (18:1n-9) through inducing stearoyl-CoA desaturase (SCD). Despite abundant studies on the regulation of SCD in the liver, little is known about this issue in the small intestine. The present study aimed to investigate the effect of clofibric acid on the fatty acid profile, particularly monounsaturated fatty acids (MUFA), and the SCD expression in intestinal mucosa. Treatment of rats with a diet containing 0.5% (w/w) clofibric acid for 7 days changed the MUFA profile of total lipids in intestinal mucosa; the proportion of 18:1n-9 was significantly increased, whereas those of palmitoleic (16:1n-7) and cis-vaccenic (18:1n-7) acids were not changed. Upon the treatment with clofibric acid, SCD was induced and the gene expression of SCD1, SCD2, and fatty acid elongase (Elovl) 6 was up-regulated, but that of Elovl5 was unaffected. Fat-free diet feeding for 28 days increased the proportions of 16:1n-7 and 18:1n-7, but did not effectively change that of 18:1n-9, in intestinal mucosa. Fat-free diet feeding up-regulated the gene expression of SCD1, but not that of SCD2, Elovl6, or Elovl5. These results indicate that intestinal mucosa significantly changes its MUFA profile in response to challenges by clofibric acid and a fat-free diet and suggest that up-regulation of the gene expression of SCD along with Elovl6 is indispensable to elevate the proportion of 18:1n-9 in intestinal mucosa.

  12. Lesion-induced pseudo-dominance at functional magnetic resonance imaging: implications for preoperative assessments.

    Science.gov (United States)

    Ulmer, John L; Hacein-Bey, Lotfi; Mathews, Vincent P; Mueller, Wade M; DeYoe, Edgar A; Prost, Robert W; Meyer, Glenn A; Krouwer, Hendrikus G; Schmainda, Kathleen M

    2004-09-01

    To illustrate how lesion-induced neurovascular uncoupling at functional magnetic resonance imaging (fMRI) can mimic hemispheric dominance opposite the side of a lesion preoperatively. We retrospectively reviewed preoperative fMRI mapping data from 50 patients with focal brain abnormalities to establish patterns of hemispheric dominance of language, speech, visual, or motor system functions. Abnormalities included gliomas (31 patients), arteriovenous malformations (AVMs) (11 patients), other congenital lesions (4 patients), encephalomalacia (3 patients), and tumefactive encephalitis (1 patient). A laterality ratio of fMRI hemispheric dominance was compared with actual hemispheric dominance as verified by electrocortical stimulation, Wada testing, postoperative and posttreatment deficits, and/or lesion-induced deficits. fMRI activation maps were generated with cross-correlation (P frontal gyrus gliomas and in one patient with focal tumefactive meningoencephalitis, fMRI incorrectly suggested strong right hemispheric speech dominance. In two patients with lateral precentral gyrus region gliomas and one patient with a left central sulcus AVM, the fMRI pattern incorrectly suggested primary corticobulbar motor dominance contralateral to the side of the lesion. In a patient with a right superior frontal gyrus AVM, fMRI revealed pronounced left dominant supplementary motor area activity in response to a bilateral complex motor task, but right superior frontal gyrus perilesional hemorrhage and edema subsequently caused left upper-extremity plegia. Pathophysiological factors that might have caused neurovascular uncoupling and facilitated pseudo-dominance at fMRI in these patients included direct tumor infiltration, neovascularity, cerebrovascular inflammation, and AVM-induced hemodynamic effects. Sixteen patients had proven (1 patient), probable (2 patients), or possible (13 patients) but unproven lesion-induced homotopic cortical reorganization. Lesion-induced neurovascular

  13. Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells

    Science.gov (United States)

    2010-01-01

    Background Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD) in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'). To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria. Results C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase). Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics. Conclusion These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients. PMID:21040540

  14. Campylobacter jejuni induces transcytosis of commensal bacteria across the intestinal epithelium through M-like cells

    Directory of Open Access Journals (Sweden)

    Kalischuk Lisa D

    2010-11-01

    Full Text Available Abstract Background Recent epidemiological analyses have implicated acute Campylobacter enteritis as a factor that may incite or exacerbate inflammatory bowel disease (IBD in susceptible individuals. We have demonstrated previously that C. jejuni disrupts the intestinal barrier function by rapidly inducing epithelial translocation of non-invasive commensal bacteria via a transcellular lipid raft-mediated mechanism ('transcytosis'. To further characterize this mechanism, the aim of this current study was to elucidate whether C. jejuni utilizes M cells to facilitate transcytosis of commensal intestinal bacteria. Results C. jejuni induced translocation of non-invasive E. coli across confluent Caco-2 epithelial monolayers in the absence of disrupted transepithelial electrical resistance or increased permeability to a 3 kDa dextran probe. C. jejuni-infected monolayers displayed increased numbers of cells expressing the M cell-specific marker, galectin-9, reduced numbers of enterocytes that stained with the absorptive enterocyte marker, Ulex europaeus agglutinin-1, and reduced activities of enzymes typically associated with absorptive enterocytes (namely alkaline phosphatase, lactase, and sucrase. Furthermore, in Campylobacter-infected monolayers, E. coli were observed to be internalized specifically within epithelial cells displaying M-like cell characteristics. Conclusion These data indicate that C. jejuni may utilize M cells to promote transcytosis of non-invasive bacteria across the intact intestinal epithelial barrier. This mechanism may contribute to the inflammatory immune responses against commensal intestinal bacteria commonly observed in IBD patients.

  15. Splenectomy attenuates severe thermal trauma-induced intestinal barrier breakdown in rats.

    Science.gov (United States)

    Liu, Xiang-dong; Chen, Zhen-yong; Yang, Peng; Huang, Wen-guang; Jiang, Chun-fang

    2015-12-01

    The severe local thermal trauma activates a number of systemic inflammatory mediators, such as TNF-α, NF-κB, resulting in a disruption of gut barrier. The gastrointestinal tight junction (TJ) is highly regulated by membrane-associated proteins including zonula occludens protein-1 (ZO-1) and occludin, which can be modulated by inflammatory cytokines. As splenectomy has been shown to reduce secretion of cytokines, we hypothesized that (1) severe scald injury up-regulates TNF-α and NF-κB, meanwhile down-regulates expression of ZO-1 and occludin, leading to the increased intestinal permeability, and (2) splenectomy can prevent the burn-induced decrease in ZO-1 and occludin expression, resulting in improved intestinal barrier. Wistar rats undergoing a 30% total body surface area (TBSA) thermal trauma were randomized to receive an accessorial splenectomy meanwhile or not. Intestinal injury was assessed by histological morphological analysis, and serum endotoxin levels, TNF-α, NF-κB, ZO-1 and occludin levels were detected by Western blotting in the terminal ileum mucosal tissue. 30% TBSA burn caused a significant increase in serum endotoxin levels, but NF-κB, and TNF-α, and the average intestinal villus height and mucosal thickness were decreased significantly. Burn injury could also markedly decrease the levels of ZO-1 and occludin in terminal ileum mucosal tissue (all PSplenectomy at 7th day after burn significantly reversed the burn-induced breakdown of ZO-1 and occludin (all PSplenectomy may provide a therapeutic benefit in restoring burn-induced intestinal barrier by decreasing the release of inflammatory cytokines and recovering TJ proteins.

  16. Chemotherapy induced intestinal mucositis; from bench to bed

    NARCIS (Netherlands)

    B.A.E. Koning, de (Barbara)

    2008-01-01

    textabstractPart 1 focuses primarily on the pathophysiology of mucositis, in order to gain more insight different experimental mouse models were used. Chapter 2 describes mucositis induced by high dose doxorubicin (DOX)- treatment. DOX is a frequently used cytostatic drug in childhood cancer,

  17. Lead and radiation induced hepatic lesions in Swiss albino mice and their inhibition by vitamin E

    International Nuclear Information System (INIS)

    Gajawat, Sunita; Goyal, P.K.

    2002-01-01

    The present study has been carried out to access the protective role of vitamin E against hepato-toxicity induced by lead and radiation. The present study demonstrates that the application of vitamin E prior to lead and gamma radiation exposure is quite potential to provide protection against hepatic lesions induced by such teratogens

  18. Exogenous HIV-1 Nef upsets the IFN-γ-induced impairment of human intestinal epithelial integrity.

    Directory of Open Access Journals (Sweden)

    Maria Giovanna Quaranta

    Full Text Available The mucosal tissues play a central role in the transmission of HIV-1 infection as well as in the pathogenesis of AIDS. Despite several clinical studies reported intestinal dysfunction during HIV infection, the mechanisms underlying HIV-induced impairments of mucosal epithelial barrier are still unclear. It has been postulated that HIV-1 alters enterocytic function and HIV-1 proteins have been detected in several cell types of the intestinal mucosa. In the present study, we analyzed the effect of the accessory HIV-1 Nef protein on human epithelial cell line.We used unstimulated or IFN-γ-stimulated Caco-2 cells, as a model for homeostatic and inflamed gastrointestinal tracts, respectively. We investigated the effect of exogenous recombinant Nef on monolayer integrity analyzing its uptake, transepithelial electrical resistance, permeability to FITC-dextran and the expression of tight junction proteins. Moreover, we measured the induction of proinflammatory mediators. Exogenous Nef was taken up by Caco-2 cells, increased intestinal epithelial permeability and upset the IFN-γ-induced reduction of transepithelial resistance, interfering with tight junction protein expression. Moreover, Nef inhibited IFN-γ-induced apoptosis and up-regulated TNF-α, IL-6 and MIP-3α production by Caco-2 cells while down-regulated IL-10 production. The simultaneous exposure of Caco-2 cells to Nef and IFN-γ did not affect cytokine secretion respect to untreated cells. Finally, we found that Nef counteracted the IFN-γ induced arachidonic acid cascade.Our findings suggest that exogenous Nef, perturbing the IFN-γ-induced impairment of intestinal epithelial cells, could prolong cell survival, thus allowing for accumulation of viral particles. Our results may improve the understanding of AIDS pathogenesis, supporting the discovery of new therapeutic interventions.

  19. Transplantation of hamster lung lesions induced by 239PuO2 or benz(a)pyrene

    International Nuclear Information System (INIS)

    McDonald, K.E.; Sanders, C.L.

    1980-01-01

    None(0%) of 1000 recipients of lung lesions for 239 PuO 2 -exposed hamsters that were transplanted into other hamsters' cheek pouches, developed tumors, whereas 90% of transplants from benz(a)pyrene-induced lung lesions were malignant

  20. Detection and repair of a UV-induced photosensitive lesion in the DNA of human cells

    International Nuclear Information System (INIS)

    Francis, A.A.; Regan, J.D.

    1986-01-01

    Irradiation with UV light results in damage to the DNA of human cells. The most numerous lesions are pyrimidine dimers; however, other lesions are known to occur and may contribute to the overall deleterious effect of UV irradiation. The authors have observed evidence of a UV-induced lesion other than pyrimidine dimers in the DNA of human cells by measuring DNA strand breaks induced by irradiating with 313-nm light following UV (254-nm) irradiation. The data suggest that, in normal cells, the lesion responsible for this effect is rapidly repaired or altered; whereas, in xeroderma pigmentosum variant cells it seems to remain unchanged. Some change apparently occurs in the DNA of xeroderma pigmentosum group A cells which results in an increase in photolability. These data indicate a deficiency in DNA repair of xeroderma pigmentosum variant cells as well as in xeroderma pigmentosum group A cells. (Auth.)

  1. X-irradiation-induced nuclear lesions in cultured mammaliam cells: an ultrastructural analysis

    International Nuclear Information System (INIS)

    Barham, S.S.; Walters, R.A.

    1978-01-01

    Electron-dense chromatin aggregates, hereafter referred to as lesions, have been characterized morphologically within interphase nuclei of Chinese hamster cells (line CHO) after a single acute exposure to 400, 800, 1200, or 2000 rad of x irradiation. At all doses studied, lesions were observed only after termination of radiation-induced division delay. Cell profiles were scored by electron microscopy for the presence or absence of nuclear lesions at various times after irradiation. The mitotic fraction from each irradiated population was also scored for each sample by light and electron microscopy. From these data and from simultaneous cell-density counts for each sample, it is apparent that postirradiation cell division is a prerequisite to formation of interphase nuclear lesions. Irradiated cell populations blocked in mitosis by Colcemid beyond the normal period of postirradiation division-delay failed to display nuclear lesions until after Colcemid was removed and cell division was completed. Enzyme digestions of isolated nuclei from irradiated cells with DNase I, RNase A, and Pronase suggest that the nuclear lesions are comprised primarily of chromatin. Nucleolar lesions, as well as various aberrant morphological forms of nucleoli, were also observed in cell populations after the onset of postirradiation cell division during the first 72 hr following exposure to irradiation. Delayed radiation-induced ultrastructural alterations of the nucleus included the formation of cytoplasmic invaginations into the nuclear space and inclusions of membranes within nuclei

  2. Intestinal CYP2E1: A mediator of alcohol-induced gut leakiness

    Directory of Open Access Journals (Sweden)

    Christopher B. Forsyth

    2014-01-01

    Full Text Available Chronic alcohol use can result in many pathological effects including alcoholic liver disease (ALD. While alcohol is necessary for the development of ALD, only 20–30% of alcoholics develop alcoholic steatohepatitis (ASH with progressive liver disease leading to cirrhosis and liver failure (ALD. This suggests that while chronic alcohol consumption is necessary it is not sufficient to induce clinically relevant liver damage in the absence of a secondary risk factor. Studies in rodent models and alcoholic patients show that increased intestinal permeability to microbial products like endotoxin play a critical role in promoting liver inflammation in ALD pathogenesis. Therefore identifying mechanisms of alcohol-induced intestinal permeability is important in identifying mechanisms of ALD and for designing new avenues for therapy. Cyp2e1 is a cytochrome P450 enzyme that metabolizes alcohol has been shown to be upregulated by chronic alcohol use and to be a major source of oxidative stress and liver injury in alcoholics and in animal and in vitro models of chronic alcohol use. Because Cyp2e1 is also expressed in the intestine and is upregulated by chronic alcohol use, we hypothesized it could play a role in alcohol-induced intestinal hyperpermeability. Our in vitro studies with intestinal Caco-2 cells and in mice fed alcohol showed that circadian clock proteins CLOCK and PER2 are required for alcohol-induced permeability. We also showed that alcohol increases Cyp2e1 protein and activity but not mRNA in Caco-2 cells and that an inhibitor of oxidative stress or siRNA knockdown of Cyp2e1 prevents the increase in CLOCK or PER2 proteins and prevents alcohol-induced hyperpermeability. With our collaborators we have also shown that Cyp2e1 knockout mice are resistant to alcohol-induced gut leakiness and liver inflammation. Taken together our data support a novel Cyp2e1-circadian clock protein mechanism for alcohol-induced gut leakiness that could provide new

  3. Clinical possibilities of complex probiotic Probiz for the prevention of antibiotic-associated diarrhea and other intestinal inflammatory lesions (review

    Directory of Open Access Journals (Sweden)

    Marushko Iu.V.

    2016-12-01

    Full Text Available Аntibiotic-associated diarrhea is the primary potential negative effect of antibiotic therapy. Use of complex comprising a probiotic composition in a Saccharomyces boulardii, lactobacilli and bifidobacteria is an effective method of preventing and treating antibiotic-associated diarrhea and other intestinal inflammatory diseases in children.

  4. Mast cells play no role in the pathogenesis of postoperative ileus induced by intestinal manipulation.

    Science.gov (United States)

    Gomez-Pinilla, Pedro J; Farro, Giovanna; Di Giovangiulio, Martina; Stakenborg, Nathalie; Némethova, Andrea; de Vries, Annick; Liston, Adrian; Feyerabend, Thorsten B; Rodewald, Hans-Reimer; Rodewald, Hans-Reimwer; Boeckxstaens, Guy E; Matteoli, Gianluca

    2014-01-01

    Intestinal manipulation (IM) during abdominal surgery results in intestinal inflammation leading to hypomotility or ileus. Mast cell activation is thought to play a crucial role in the pathophysiology of postoperative ileus (POI). However, this conclusion was mainly drawn using mast cell-deficient mouse models with abnormal Kit signaling. These mice also lack interstitial cells of Cajal (ICC) resulting in aberrant gastrointestinal motility even prior to surgery, compromising their use as model to study POI. To avoid these experimental weaknesses we took advantage of a newly developed knock-in mouse model, Cpa3(Cre/+) , devoid of mast cells but with intact Kit signaling. The role of mast cells in the development of POI and intestinal inflammation was evaluated assessing gastrointestinal transit and muscularis externa inflammation after IM in two strains of mice lacking mast cells, i.e. Kit(W-sh/W-sh) and Cpa3(Cre/+) mice, and by use of the mast cell stabilizer cromolyn. Kit(W-sh/W-sh) mice lack ICC networks and already revealed significantly delayed gastrointestinal transit even before surgery. IM did not further delay intestinal transit, but induced infiltration of myeloperoxidase positive cells, expression of inflammatory cytokines and recruitment of monocytes and neutrophils into the muscularis externa. On the contrary, Cpa3(Cre/+) mice have a normal network of ICC and normal gastrointestinal. Surprisingly, IM in Cpa3(Cre/+) mice caused delay in gut motility and intestinal inflammation as in wild type littermates mice (Cpa3(+/+) ). Furthermore, treatment with the mast cell inhibitor cromolyn resulted in an inhibition of mast cells without preventing POI. Here, we confirm that IM induced mast cell degranulation. However, our data demonstrate that mast cells are not required for the pathogenesis of POI in mice. Although there might be species differences between mouse and human, our results argue against mast cell inhibitors as a therapeutic approach to shorten POI.

  5. Mast cells play no role in the pathogenesis of postoperative ileus induced by intestinal manipulation.

    Directory of Open Access Journals (Sweden)

    Pedro J Gomez-Pinilla

    Full Text Available INTRODUCTION: Intestinal manipulation (IM during abdominal surgery results in intestinal inflammation leading to hypomotility or ileus. Mast cell activation is thought to play a crucial role in the pathophysiology of postoperative ileus (POI. However, this conclusion was mainly drawn using mast cell-deficient mouse models with abnormal Kit signaling. These mice also lack interstitial cells of Cajal (ICC resulting in aberrant gastrointestinal motility even prior to surgery, compromising their use as model to study POI. To avoid these experimental weaknesses we took advantage of a newly developed knock-in mouse model, Cpa3(Cre/+ , devoid of mast cells but with intact Kit signaling. DESIGN: The role of mast cells in the development of POI and intestinal inflammation was evaluated assessing gastrointestinal transit and muscularis externa inflammation after IM in two strains of mice lacking mast cells, i.e. Kit(W-sh/W-sh and Cpa3(Cre/+ mice, and by use of the mast cell stabilizer cromolyn. RESULTS: Kit(W-sh/W-sh mice lack ICC networks and already revealed significantly delayed gastrointestinal transit even before surgery. IM did not further delay intestinal transit, but induced infiltration of myeloperoxidase positive cells, expression of inflammatory cytokines and recruitment of monocytes and neutrophils into the muscularis externa. On the contrary, Cpa3(Cre/+ mice have a normal network of ICC and normal gastrointestinal. Surprisingly, IM in Cpa3(Cre/+ mice caused delay in gut motility and intestinal inflammation as in wild type littermates mice (Cpa3(+/+ . Furthermore, treatment with the mast cell inhibitor cromolyn resulted in an inhibition of mast cells without preventing POI. CONCLUSIONS: Here, we confirm that IM induced mast cell degranulation. However, our data demonstrate that mast cells are not required for the pathogenesis of POI in mice. Although there might be species differences between mouse and human, our results argue against mast

  6. Kampo medicine "Dai-kenchu-to" prevents CPT-11-induced small-intestinal injury in rats.

    Science.gov (United States)

    Chikakiyo, Motoya; Shimada, Mitsuo; Nakao, Toshihiro; Higashijima, Jun; Yoshikawa, Kozo; Nishioka, Masanori; Iwata, Takashi; Kurita, Nobuhiro

    2012-01-01

    The key anticancer agent, CPT-11 (irinotecan hydrochloride), induces severe diarrhea clinically. We investigated the effect of a Kampo medicine, Dai-kenchu-to (DKT), on CPT-11-induced intestinal injuries in rats. Twenty-four male Wistar rats were divided into three groups: a control group; a CPT-11 group, given CPT-11 150 mg/kg intraperitoneally for 2 days; and a DKT group, given DKT 300 mg/kg orally for 5 days with CPT-11 150 mg/kg intraperitoneally on days 4 and 5. The rats were killed on day 6. Interleukin (IL)-1β, IL-12, interferon (IFN)-γ, and tumor necrosis factor-α expression in the small intestine of the CPT-11 group was significantly higher than that of the control group. Interleukin-1β and IFN-γ expression was improved significantly by DKT (P DKT (P DKT suppressed CPT-11 induced inflammatory cytokines and apoptosis in the intestinal mucosa and maintained the mucosal integrity.

  7. Combined compared to dissociated oral and intestinal sucrose stimuli induce different brain hedonic processes

    Science.gov (United States)

    Clouard, Caroline; Meunier-Salaün, Marie-Christine; Meurice, Paul; Malbert, Charles-Henri; Val-Laillet, David

    2014-01-01

    The characterization of brain networks contributing to the processing of oral and/or intestinal sugar signals in a relevant animal model might help to understand the neural mechanisms related to the control of food intake in humans and suggest potential causes for impaired eating behaviors. This study aimed at comparing the brain responses triggered by oral and/or intestinal sucrose sensing in pigs. Seven animals underwent brain single photon emission computed tomography (99mTc-HMPAO) further to oral stimulation with neutral or sucrose artificial saliva paired with saline or sucrose infusion in the duodenum, the proximal part of the intestine. Oral and/or duodenal sucrose sensing induced differential cerebral blood flow changes in brain regions known to be involved in memory, reward processes and hedonic (i.e., pleasure) evaluation of sensory stimuli, including the dorsal striatum, prefrontal cortex, cingulate cortex, insular cortex, hippocampus, and parahippocampal cortex. Sucrose duodenal infusion only and combined sucrose stimulation induced similar activity patterns in the putamen, ventral anterior cingulate cortex and hippocampus. Some brain deactivations in the prefrontal and insular cortices were only detected in the presence of oral sucrose stimulation. Finally, activation of the right insular cortex was only induced by combined oral and duodenal sucrose stimulation, while specific activity patterns were detected in the hippocampus and parahippocampal cortex with oral sucrose dissociated from caloric load. This study sheds new light on the brain hedonic responses to sugar and has potential implications to unravel the neuropsychological mechanisms underlying food pleasure and motivation. PMID:25147536

  8. Pulmonary lesions induced by inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Dagle, G.E.; Lund, J.E.; Park, J.F.

    1976-01-01

    The histopathologic features of pulmonary fibrosis and bronchiolo-alveolar carcinoma in beagles exposed to aerosols of 238 Pu or 239 Pu oxide are reviewed. A hypothesis of the pathogenesis of radiation pneumonitis induced by inhalation of plutonium oxide is presented; this hypothesis included phagocytosis of Pu particles, fibrosis responding to the necrosis, and alveolar cell hyperplasia compensating for alveolar cells killed by alpha radiation. Histopathologic features of the epithelial changes suggest a progression from hyperplasia to metaplasia and, finally, to bronchiolo-alveolar carcinoma. The possibility of concurrent radiation-induced lymphopenia contributing to the development of bronchiolo-alveolar carcinoma through a loss of immunologic surveillance is discussed

  9. Pulmonary lesions induced by inhaled plutonium in beagles

    International Nuclear Information System (INIS)

    Dagle, G.E.; Lund, J.E.; Park, J.F.

    1975-01-01

    The histopathologic features of pulmonary fibrosis and bronchiolo-alveolar carcinoma in beagles exposed to aerosols of plutonium oxide were reviewed. A hypothesis of the pathogenesis of radiation pneumonitis induced by inhalation of plutonium oxide was presented; this hypothesis included phagocytosis of plutonium particles, fibrosis responding to the necrosis, and alveolar cell hyperplasia compensating for alveolar cells killed by alpha radiation. Histopathologic features of the epithelial changes suggest a progression from hyperplasia to metaplasia and, finally, to bronchiolo-alveolar carcinoma. The possibility of concurrent radiation-induced lymphopenia contributing to the development of bronchiolo-alveolar carcinoma through a loss of immunologic surveillance was discussed

  10. Intestinal metaplasia induced by x-irradiation in different strains of rats

    International Nuclear Information System (INIS)

    Watanabe, Hiromitsu; Naito, Masashi; Kawashima, Kengo; Ito, Akihiro

    1985-01-01

    Attempts were made to examine strain differences in the susceptibility of rats to intestinal metaplasia induced by X-irradiation. The gastric regions of 4 inbred male rats (SHR, F344, WKY, and LEW strains) in 5-week-old and 2 random bred male rats (SD, and WIS strains) were irradiated with a total dose of 20 Gy X-ray given in two equal fractions separated by three days. Upon sacrifice at 6 months after the last irradiation, the number of intestinal metaplastic crypts with positive reaction to alkaline phosphatase (ALP) appeared highest in the SHR and lowest in the WIS rats. Morphologically, the number of crypts with intestinal metaplasia in whole glandular stomachs of SHR, WIS, F344, and SD rats were higher than those in WKY and LEW rats. In the pyloric gland, it was highest in WIS rats, while in the fundic gland it was highest in SHR rats. The results show that the appearance and location of intestinal metaplasia by X-irradiation are greatly influenced by the strain of the rat. (author)

  11. RECENT ADVANCES IN STRATEGIES FOR IMMUNOTHERAPY OF HUMAN PAPILLOMAVIRUS-INDUCED LESIONS

    Science.gov (United States)

    Kanodia, Shreya; Da Silva, Diane M.; Kast, W. Martin

    2016-01-01

    Human papillomavirus (HPV)-induced lesions are distinct in that they have targetable foreign antigens, the expression of which is necessary to maintain the cancerous phenotype. Hence, they pose as a very attractive target for “proof of concept” studies in the development of therapeutic vaccines. This review will focus on the most recent clinical trials for the immunotherapy of mucosal and cutaneous HPV-induced lesions as well as emerging therapeutic strategies that have been tested in pre-clinical models for HPV-induced lesions. Progress in peptide-based vaccines, DNA-based vaccines, viral/bacterial vector-based vaccines, immune response modifiers, photodynamic therapy and T cell receptor based therapy for HPV will be discussed. PMID:17973257

  12. Radiation induced testicular lesions and their modification by vitamin E

    International Nuclear Information System (INIS)

    Pareek, T.K.; Gajawat, S.; Singh, N.; Goyal, P.K.; Dev, P.K.

    2001-01-01

    Man is subjected to radiation exposure from cosmic rays and radioactivity from soil; apart from these natural sources of radiation, diagnostic and therapeutic radiological procedures are the largest source of radiation dose to human beings. These radiations have been shown to cause lesions in various mammalian tissues and organs. Testis is one of the most radiosensitive organs because of its cell renewal system. A number of chemical compounds have been and are being tested for their radioprotective effects on different animals. The antioxidant nature of Vitamin E and its role in maintenance of member structure suggests the presumptive radioprotective nature of this vitamin as well as its possible role in repair of radiation damage. In spite of some controversial reports, the radioprotective effect of Vitamin E has been observed by some investigators. In the light of above, the present study has been undertaken to assess the presumptive prophylactic effects of Vitamin E on the testes of Swiss albino mice subjected to sub-lethal whole-body gamma radiations

  13. High fructose intake fails to induce symptomatic adaptation but may induce intestinal carriers

    Directory of Open Access Journals (Sweden)

    Debra Heilpern

    2010-01-01

    Full Text Available Fructose has several interactions in man, including intolerance and promotion of some diseases. However, fructose in fruits and in prebiotics may be associated with benefits. Adaptation to regular fructose ingestion as defined for lactose could support a beneficial rather than a deleterious effect. This study was undertaken to evaluate symptomatic response and potential underlying mechanisms of fecal bacterial change and breath hydrogen response to short term regular fructose supplementation. Forty-five participants were recruited for a 3 day recall diet questionnaire and a 50 g fructose challenge. Breath hydrogen was measured for 4.5 hrs and symptoms were recorded. Thirty-eight subjects provided stool samples for analysis by selective culture of 4 groups of bacteria, including bifidobacteria and lactobacilli. Intolerant subjects returned a second time 15 days later. Ten of these served as controls and 16 received 30 g fructose twice a day. Ten of the latter returned 27 days later, after stopping fructose for a third challenge test. Student’s paired, unpaired t-tests and Pearson correlations were used. Significance was accepted at P<0.05. After fructose rechallenge there were no significant reductions in symptoms scores in volunteers in either the fructose supplemented or non supplemented groups. However, total breath hydrogen was reduced between test 1 and test 2 (P=0.03 or test 3 (P=0.04 in the group given fructose then discontinued, compared with controls. There were no statistically significant changes in bacterial numbers between test 2 and 1. This study shows that regular consumption of high dose fructose does not follow the lactose model of adaptation. Observed changes in hydrogen breath tests raise the possibility that intestinal carriers of fructose may be induced potentially aggravating medical problems attributed to fructose.

  14. Soya-saponins induce intestinal inflammation and barrier dysfunction in juvenile turbot (Scophthalmus maximus).

    Science.gov (United States)

    Gu, Min; Jia, Qian; Zhang, Zhiyu; Bai, Nan; Xu, Xiaojie; Xu, Bingying

    2018-06-01

    Soybean meal-induced enteritis (SBMIE) is a well-described condition in the distal intestine (DI) of several cultured fish species, but the exact cause is still unclear. The work on Atlantic salmon and zebrafish suggested soya-saponins, as heat-stable anti-nutritional factors in soybean meal, are the major causal agents. However, this conclusion was not supported by the research on some other fish, such as gilthead sea bream and European sea bass. Our previous work proved that soybean could induce SBMIE on turbot and the present work aimed to investigate whether soya-saponins alone could cause SBMIE and the effects of soya-saponins on the intestinal barrier function in juvenile turbot. Turbots with initial weight 11.4 ± 0.02 g were fed one of four fishmeal-based diets containing graded levels of soya-saponins (0, 2.5, 7.5, 15 g kg -1 ) for 8 weeks. At the end of the trial, all fish were weighed and plasma was obtained for diamine oxidase (DAO) activity and d-lactate level analysis and DI was sampled for histological evaluation and quantification of antioxidant parameters and inflammatory marker genes. The activities of superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase and intestinal glutathione level were selected to evaluated intestinal antioxidant system. The distal intestinal epithelial cell (IEC) proliferation and apoptosis were investigated by proliferating cell nuclear antigen (PCNA) labelling and TdT-mediated dUTP nick end labeling (TUNEL), respectively. The results showed that soya-saponins caused significantly dose-dependent decrease in the growth performance and nutrient utilization (p soya-saponins. Significantly dose-dependent increases in severity of the inflammation concomitant with up-regulated expression of il-1β, il-8, and tnf-α, increased IEC proliferation and apoptosis, and decreases in selected antioxidant parameters were detected (p soya-saponins (p soya-saponins induced enteritis and compromised

  15. Inhibition of IKKβ in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality.

    Science.gov (United States)

    Dominguez, Jessica A; Samocha, Alexandr J; Liang, Zhe; Burd, Eileen M; Farris, Alton B; Coopersmith, Craig M

    2013-10-01

    Nuclear factor-κB is a critical regulator of cell-survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase. Prospective, randomized controlled study. Animal laboratories in university medical centers. Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkβ) and wild-type mice were subjected to sham laparotomy or cecal ligation and puncture. Animals were killed at 24 hours or followed 7 days for survival. Septic wild-type mice had decreased villus length compared with sham mice, whereas villus atrophy was further exacerbated in septic Vil-Cre/Ikkβ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared with sham mice, which was further exacerbated in Vil-Cre/Ikkβ mice. Sepsis induced intestinal hyperpermeability in wild-type mice compared with sham mice, which was further exacerbated in septic Vil-Cre/Ikkβ mice. This was associated with increased intestinal expression of claudin-2 in septic wild-type mice, which was further increased in septic Vil-Cre/Ikkβ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following cecal ligation and puncture, and interleukin 10 and monocyte chemoattractant protein-1 levels were higher in septic Vil-Cre/Ikkβ mice than in septic wild-type mice. All septic mice were bacteremic, but no differences in bacterial load were identified between wild-type and Vil-Cre/Ikkβ mice. To determine the functional significance of these results, animals were followed for survival. Septic wild-type mice had lower mortality than septic Vil-Cre/Ikkβ mice (47% vs 80%, p<0.05). Antitumor necrosis factor administration decreased intestinal apoptosis, permeability, and mortality in wild-type septic mice, and a similar improvement in intestinal integrity and survival were seen when antitumor necrosis factor was given to Vil-Cre/Ikkβ mice. Enterocyte

  16. Inhibition of IKKß in enterocytes exacerbates sepsis-induced intestinal injury and worsens mortality

    Science.gov (United States)

    Dominguez, Jessica A.; Samocha, Alexandr J.; Liang, Zhe; Burd, Eileen M.; Farris, Alton B.; Coopersmith, Craig M.

    2013-01-01

    Objective NF-kB is a critical regulator of cell survival genes and the host inflammatory response. The purpose of this study was to investigate the role of enterocyte-specific NF-kB in sepsis through selective ablation of IkB kinase (IKK)-ß. Design Prospective, randomized, controlled study. Setting Animal laboratories in university medical centers. Subjects and Interventions Mice lacking functional NF-kB in their intestinal epithelium (Vil-Cre/Ikkßf/Δ) and wild type (WT) mice were subjected to sham laparotomy or cecal ligation and puncture (CLP). Animals were sacrified at 24 hours or followed seven days for survival. Measurements and Main Results Septic WT mice had decreased villus length compared to sham mice while villus atrophy was further exacerbated in septic Vil-Cre/Ikkßf/Δ mice. Sepsis induced an increase in intestinal epithelial apoptosis compared to sham mice which was further exacerbated in Vil-Cre/Ikkßf/Δ mice. Sepsis induced intestinal hyperpermeability in WT mice compared to sham mice, which was further exacerbated in septic Vil-Cre/Ikkßf/Δ mice. This was associated with increased intestinal expression of claudin-2 in septic WT mice, which was further increased in septic Vil-Cre/Ikkßf/Δ mice. Both, pro-inflammatory and anti-inflammatory cytokines were increased in serum following CLP, and IL-10 and MCP-1 levels were higher in septic Vil-Cre/Ikkßf/Δ mice than septic WT mice. All septic mice were bacteremic, but no differences in bacterial load were identified between WT and Vil-Cre/Ikkßf/Δ mice. To determine the functional significance of these results, animals were followed for survival. Septic WT mice had lower mortality than septic Vil-Cre/Ikkßf/Δ mice (47% vs. 80%, p<0.05). Anti-TNF administration decreased intestinal apoptosis, permeability and mortality in WT septic mice and a similar improvement in intestinal integrity and survival were seen when anti-TNF was given to Vil-Cre/Ikkßf/Δ mice. Conclusions Enterocyte-specific NF

  17. Ectopic intestinal glands after segmental small bowel irradiation in the cat

    International Nuclear Information System (INIS)

    Rubio, C.A.; Eriksson, B.; Johnsson, L.

    1983-01-01

    Following segmental irradiation of the small bowel, 5 of 64 cats demonstrated ectopic intestinal glands in the submucosal tissue. In addition, one of these 5 cats had foci of abnormal glands in the muscularis mucosae. In 2 of the 5 animals, cellular polymorphism, nucleolar irregularity and loss of cellular polarity were present in irradiation-induced ectopic intestinal glands. The review of the literature indicates that intestinal irradiation may induce intestinal adenocarcinomas with metastatic growth. The possibility that ectopic intestinal glands are precancerous lesions in the irradiated cat is discussed. (Auth.)

  18. Appearance of radiation-induced lesions after radiotherapy for Hodgkin's disease of the mediastinum and lungs

    Energy Technology Data Exchange (ETDEWEB)

    Zomer-Drozda, J [Instytut Onkologii, Warsaw (Poland)

    1976-01-01

    The incidence of radiation-induced lesions of lung tissue adjacent to the mediastinum and covered by radiation was established on the basis of a retrospective analysis of radiograms of 245 patients treated at the Institute of Oncology in Warsaw in the years 1951-1968, who received radiotherapy to the mediastinal lymph nodes. The radiation-induced lesions were divided into 4 grades depending on their extent and intensity of pulmonary tissue damage. Criteria for classification of radiation-induced fibrosis into the above mentioned grades were established. The correlation between radiation-induced injury and the doses of X-rays applied to the mediastinal lymph nodes was analysed. The importance of radiation-induced changes in the mediastinum and lungs for the diagnosis of recurrences in the irradiated fields, in the marginal areas and granulomatous infiltrations in pulmonary tissue is discussed.

  19. Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3.

    Science.gov (United States)

    Lammers, Karen M; Lu, Ruliang; Brownley, Julie; Lu, Bao; Gerard, Craig; Thomas, Karen; Rallabhandi, Prasad; Shea-Donohue, Terez; Tamiz, Amir; Alkan, Sefik; Netzel-Arnett, Sarah; Antalis, Toni; Vogel, Stefanie N; Fasano, Alessio

    2008-07-01

    Celiac disease is an immune-mediated enteropathy triggered by gliadin, a component of the grain protein gluten. Gliadin induces an MyD88-dependent zonulin release that leads to increased intestinal permeability, a postulated early element in the pathogenesis of celiac disease. We aimed to establish the molecular basis of gliadin interaction with intestinal mucosa leading to intestinal barrier impairment. Alpha-gliadin affinity column was loaded with intestinal mucosal membrane lysates to identify the putative gliadin-binding moiety. In vitro experiments with chemokine receptor CXCR3 transfectants were performed to confirm binding of gliadin and/or 26 overlapping 20mer alpha-gliadin synthetic peptides to the receptor. CXCR3 protein and gene expression were studied in intestinal epithelial cell lines and human biopsy specimens. Gliadin-CXCR3 interaction was further analyzed by immunofluorescence microscopy, laser capture microscopy, real-time reverse-transcription polymerase chain reaction, and immunoprecipitation/Western blot analysis. Ex vivo experiments were performed using C57BL/6 wild-type and CXCR3(-/-) mouse small intestines to measure intestinal permeability and zonulin release. Affinity column and colocalization experiments showed that gliadin binds to CXCR3 and that at least 2 alpha-gliadin 20mer synthetic peptides are involved in this binding. CXCR3 is expressed in mouse and human intestinal epithelia and lamina propria. Mucosal CXCR3 expression was elevated in active celiac disease but returned to baseline levels following implementation of a gluten-free diet. Gliadin induced physical association between CXCR3 and MyD88 in enterocytes. Gliadin increased zonulin release and intestinal permeability in wild-type but not CXCR3(-/-) mouse small intestine. Gliadin binds to CXCR3 and leads to MyD88-dependent zonulin release and increased intestinal permeability.

  20. Intestine-Specific Mttp Deletion Decreases Mortality and Prevents Sepsis-Induced Intestinal Injury in a Murine Model of Pseudomonas aeruginosa Pneumonia

    Science.gov (United States)

    Dominguez, Jessica A.; Xie, Yan; Dunne, W. Michael; Yoseph, Benyam P.; Burd, Eileen M.; Coopersmith, Craig M.; Davidson, Nicholas O.

    2012-01-01

    Background The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the “motor” of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO), which exhibit a block in chylomicron assembly together with lipid malabsorption. Methodology/Principal Findings Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0%) dying compared to 5/17 (29%) control mice (p<0.05). This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL) levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice. Conclusions/Significance These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by

  1. Intestine-specific Mttp deletion decreases mortality and prevents sepsis-induced intestinal injury in a murine model of Pseudomonas aeruginosa pneumonia.

    Directory of Open Access Journals (Sweden)

    Jessica A Dominguez

    Full Text Available The small intestine plays a crucial role in the pathophysiology of sepsis and has been referred to as the "motor" of the systemic inflammatory response. One proposed mechanism is that toxic gut-derived lipid factors, transported in mesenteric lymph, induce systemic injury and distant organ failure. However, the pathways involved are yet to be defined and the role of intestinal chylomicron assembly and secretion in transporting these lipid factors is unknown. Here we studied the outcome of sepsis in mice with conditional, intestine-specific deletion of microsomal triglyceride transfer protein (Mttp-IKO, which exhibit a block in chylomicron assembly together with lipid malabsorption.Mttp-IKO mice and controls underwent intratracheal injection with either Pseudomonas aeruginosa or sterile saline. Mttp-IKO mice exhibited decreased seven-day mortality, with 0/20 (0% dying compared to 5/17 (29% control mice (p<0.05. This survival advantage in Mttp-IKO mice, however, was not associated with improvements in pulmonary bacterial clearance or neutrophil infiltration. Rather, Mttp-IKO mice exhibited protection against sepsis-associated decreases in villus length and intestinal proliferation and were also protected against increased intestinal apoptosis, both central features in control septic mice. Serum IL-6 levels, a major predictor of mortality in human and mouse models of sepsis, were elevated 8-fold in septic control mice but remained unaltered in septic Mttp-IKO mice. Serum high density lipoprotein (HDL levels were reduced in septic control mice but were increased in septic Mttp-IKO mice. The decreased levels of HDL were associated with decreased hepatic expression of apolipoprotein A1 in septic control mice.These studies suggest that strategies directed at blocking intestinal chylomicron secretion may attenuate the progression and improve the outcome of sepsis through effects mediated by metabolic and physiological adaptations in both intestinal and

  2. Association of malignancy with rapid growth in early lesions induced by irradiation of rat skin

    International Nuclear Information System (INIS)

    McGregor, J.F.

    1979-01-01

    Epithelial lesions induced by irradiation of rat skin were studied to determine (a) the relationship of malignancy to dose, (b) the types of lesions and circumstances leading to overt malignancy, and (c) the growth rates of lesions progressing to malignancy versus those of lesions remaining benign. High doses of radiation were shown to be associated with the production of epidermal cancers, the maximum yield being obtained at 6,400 rads. Conversely, a peak yield of noncancerous lesions was obtained at 1,600 rads. This association between malignancy and high dose was consistent for cancers evolving from warts, cysts, and chronic ulcers. Although the proportion of warts among the induced lesions was much higher than that of the cysts or chronic ulcers (76, 14, and 10%, respectively), the likelihood of warts becoming cancerous was substantially lower (14, 23, and 21%). The combined data for all doses showed that the latency period of the epidermal cancers was significantly (P = 0.015) shorter than that of the benign tumors. Rapid growth rates were observed for warts, cysts, and chronic ulcers progressing to overt cancer, and these did not overlap at any point on the growth scale with rates for benign tumors. This finding suggested that the potential for malignant development had been established early in the carcinogenic process, very likely at induction

  3. Co-micronized palmitoylethanolamide/polydatin treatment causes endometriotic lesion regression in a rodent model of surgically-induced endometriosis

    Directory of Open Access Journals (Sweden)

    Rosanna Di Paola

    2016-10-01

    Full Text Available Endometriosis is a chronic, painful disease characterized by the presence of endometrial glands and stroma outside the uterine cavity. Palmitoylethanolamide (PEA, an endogenous fatty acid amide, has anti-inflammatory and neuroprotective effects. PEA lacks free radical scavenging activity, unlike polydatin (PLD, a natural precursor of resveratrol. The aim of this study was to investigate the effect of orally administered co-micronized PEA/polydatin (m(PEA/PLD in an autologous rat model of surgically-induced endometriosis. Endometriosis was induced in female Wistar albino rats by auto-transplantation of uterine squares (implants into the intestinal mesentery and peritoneal cavity. Rats were distributed into one control group and one treatment group (10 animals each: m(PEA/PLD 10 mg/kg/day. At 28 days after surgery the relative volume of the endometrioma was determined. Endometrial-like tissue was confirmed by histology: Masson trichrome and toluidine blue were used to detect fibrosis and mast cells, respectively. The treated group displayed a smaller cyst diameter, with improved fibrosis score and mast cell number decrease. m(PEA/PLD administration decreased angiogenesis (vascular endothelial growth factor, nerve growth factor, intercellular adhesion molecule, matrix metalloproteinase 9 expression and lymphocyte accumulation. m(PEA/PLD treatment also reduced peroxynitrite formation, (poly-ADPribose polymerase activation, IkBα phosphorylation and nuclear facor-kB traslocation in the nucleus. Our results suggested that m(PEA/PLD may be of use to inhibit development of endometriotic lesions in rats.

  4. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Science.gov (United States)

    Liu, Dong-Hai; Huang, Xu; Guo, Xin; Meng, Xiang-Min; Wu, Yi-Song; Lu, Hong-Li; Zhang, Chun-Mei; Kim, Young-chul; Xu, Wen-Xie

    2014-01-01

    Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV) was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV) to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  5. Intestinal exposure to PCB 153 induces inflammation via the ATM/NEMO pathway.

    Science.gov (United States)

    Phillips, Matthew C; Dheer, Rishu; Santaolalla, Rebeca; Davies, Julie M; Burgueño, Juan; Lang, Jessica K; Toborek, Michal; Abreu, Maria T

    2018-01-15

    Polychlorinated biphenyls (PCBs) are persistent organic pollutants that adversely affect human health. PCBs bio-accumulate in organisms important for human consumption. PCBs accumulation in the body leads to activation of the transcription factor NF-κB, a major driver of inflammation. Despite dietary exposure being one of the main routes of exposure to PCBs, the gut has been widely ignored when studying the effects of PCBs. We investigated the effects of PCB 153 on the intestine and addressed whether PCB 153 affected intestinal permeability or inflammation and the mechanism by which this occurred. Mice were orally exposed to PCB 153 and gut permeability was assessed. Intestinal epithelial cells (IECs) were collected and evaluated for evidence of genotoxicity and inflammation. A human IEC line (SW480) was used to examine the direct effects of PCB 153 on epithelial function. NF-кB activation was measured using a reporter assay, DNA damage was assessed, and cytokine expression was ascertained with real-time PCR. Mice orally exposed to PCB 153 had an increase in intestinal permeability and inflammatory cytokine expression in their IECs; inhibition of NF-кB ameliorated both these effects. This inflammation was associated with genotoxic damage and NF-кB activation. Exposure of SW480 cells to PCB 153 led to similar effects as seen in vivo. We found that activation of the ATM/NEMO pathway by genotoxic stress was upstream of NF-kB activation. These results demonstrate that oral exposure to PCB 153 is genotoxic to IECs and induces downstream inflammation and barrier dysfunction in the intestinal epithelium. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. Voltage dependent potassium channel remodeling in murine intestinal smooth muscle hypertrophy induced by partial obstruction.

    Directory of Open Access Journals (Sweden)

    Dong-Hai Liu

    Full Text Available Partial obstruction of the small intestine causes obvious hypertrophy of smooth muscle cells and motility disorder in the bowel proximate to the obstruction. To identify electric remodeling of hypertrophic smooth muscles in partially obstructed murine small intestine, the patch-clamp and intracellular microelectrode recording methods were used to identify the possible electric remodeling and Western blot, immunofluorescence and immunoprecipitation were utilized to examine the channel protein expression and phosphorylation level changes in this research. After 14 days of obstruction, partial obstruction caused obvious smooth muscle hypertrophy in the proximally located intestine. The slow waves of intestinal smooth muscles in the dilated region were significantly suppressed, their amplitude and frequency were reduced, whilst the resting membrane potentials were depolarized compared with normal and sham animals. The current density of voltage dependent potassium channel (KV was significantly decreased in the hypertrophic smooth muscle cells and the voltage sensitivity of KV activation was altered. The sensitivity of KV currents (IKV to TEA, a nonselective potassium channel blocker, increased significantly, but the sensitivity of IKv to 4-AP, a KV blocker, stays the same. The protein levels of KV4.3 and KV2.2 were up-regulated in the hypertrophic smooth muscle cell membrane. The serine and threonine phosphorylation levels of KV4.3 and KV2.2 were significantly increased in the hypertrophic smooth muscle cells. Thus this study represents the first identification of KV channel remodeling in murine small intestinal smooth muscle hypertrophy induced by partial obstruction. The enhanced phosphorylations of KV4.3 and KV2.2 may be involved in this process.

  7. Lesions of the lateral hypothalamus impair pilocarpine-induced salivation in rats.

    Science.gov (United States)

    Renzi, A; De Luca, L A; Menani, J V

    2002-09-15

    In the present study we investigated the effects of electrolytic lesions of the lateral hypothalamus (LH) in the salivation induced by intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) injection of the cholinergic agonist pilocarpine. Rats with sham or LH lesions and stainless steel cannulas implanted into the lateral ventricle (LV) were used. In rats anesthetized with urethane (1.25mg/kg of body weight) saliva was collected using pre-weighed cotton balls inserted in the animal mouth during a period of 7 min following i.c.v. or i.p. injection of pilocarpine. Injection of pilocarpine (1mg/kg of body weight) i.p. in sham-operated rats (6h, 2, 7, and 15 days after the surgery) induced salivation (497+/-24, 452+/-26, 476+/-30, and 560+/-75 mg/7 min, respectively). The effects of i.p. pilocarpine was reduced 6h, 2 and 7 days after LH lesions (162+/-37, 190+/-32, and 229+/-27 mg/7 min, respectively), not 15 days after LH lesions (416+/-89 mg/7 min). Injection of pilocarpine (120 micro g/micro l) i.c.v., in sham-operated rats (6h, 2, 7, and 15 days after the surgery) also produced salivation (473+/-20, 382+/-16, 396+/-14, and 427+/-47 mg/7 min, respectively). The salivation induced by i.c.v. pilocarpine was also reduced 6h, 2 and 7 days after LH lesions (243+/-19, 278+/-24, and 295+/-27 mg/7 min, respectively), not 15 days after LH lesions (385+/-48 mg/7 min). The present results show the participation of the LH in the salivation induced by central or peripheral injection of pilocarpine in rats, reinforcing the involvement of central mechanisms on pilocarpine-induced salivation.

  8. Transient, heat-induced thermal resistance in the small intestine of mouse

    International Nuclear Information System (INIS)

    Hume, S.P.; Marigold, J.C.L.

    1980-01-01

    Heat-induced thermal resistance has been investigated in mouse jejunum by assaying crypt survival 24 h after treatment. Hyperthermia was achieved by immersing an exteriorized loop of intestine in a bath of Krebs-Ringer solution. Two approaches have been used. In the first, thermal survival curves were obtained following single hyperthermal treatments at temperatures in the range 42 to 44 0 C. Transient thermal resistance, inducted by a plateau in the crypt survival curve, developed during heating at temperatures around 42.5 0 C after 60 to 80 min. In the second series of experiments, a priming heat treatment (40.0, 41.0, 41.5, or 42.0 0 C for 60 min) was followed at varying intervals by a test treatment at 43.0 0 C. A transient resistance to the second treatment was induced, the extent and time of development being dependent upon the priming treatment. Crypt survival curves for thermally resistant intestine showed an increase in thermal D 0 and a decrease in n compared with curves from previously unheated intestine

  9. Claudin-3 expression in radiation-exposed rat models: A potential marker for radiation-induced intestinal barrier failure

    Energy Technology Data Exchange (ETDEWEB)

    Shim, Sehwan; Lee, Jong-geol; Bae, Chang-hwan; Lee, Seung Bum [National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Jang, Won-Suk; Lee, Sun-Joo [Laboratory of Experimental Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Lee, Seung-Sook [National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Department of Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of); Park, Sunhoo, E-mail: sunhoo@kcch.re.kr [National Radiation Emergency Medical Center, Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of); Department of Pathology, Korea Cancer Center Hospital, Seoul (Korea, Republic of)

    2015-01-02

    Highlights: • Irradiation increased intestinal bacterial translocation, accompanied by claudin protein expression in rats. • Neurotensin decreased the bacterial translocation and restored claudin-3 expression. • Claudin-3 can be used as a marker in evaluating radiation induced intestinal injury. - Abstract: The molecular events leading to radiation-induced intestinal barrier failure are not well known. The influence of the expression of claudin proteins in the presence and absence of neurotensin was investigated in radiation-exposed rat intestinal epithelium. Wistar rats were randomly divided into control, irradiation, and irradiation + neurotensin groups, and bacterial translocation to the mesenteric lymph node and expression of claudins were determined. Irradiation led to intestinal barrier failure as demonstrated by significant bacterial translocation. In irradiated terminal ilea, expression of claudin-3 and claudin-4 was significantly decreased, and claudin-2 expression was increased. Administration of neurotensin significantly reduced bacterial translocation and restored the structure of the villi as seen by histologic examination. Among the three subtype of claudins, only claudin-3 expression was restored. These results suggest that the therapeutic effect of neurotensin on the disruption of the intestinal barrier is associated with claudin-3 alteration and that claudin-3 could be used as a marker in evaluating radiation-induced intestinal injury.

  10. Aeromonas caviae strain induces Th1 cytokine response in mouse intestinal tract

    Energy Technology Data Exchange (ETDEWEB)

    Hayes, S L; Lye, D J; McKinstry, Craig A.; Vesper, Sephen J.

    2010-01-01

    Aeromonas caviae has been associated with human gastrointestinal disease. Strains of this species typically lack virulence factors (VFs) such as enterotoxins and hemolysins that are produced by other human pathogens of the Aeromonas genus. Microarray profiling of murine small intestinal extracts, 24 hours after oral infection with an A. caviae strain, provides evidence of a Th1 type immune response. A large number of gamma-interferon (γ-IFN) induced genes are up-regulated as well as several tumor necrosis factor-alpha (TNF-α) transcripts. A. caviae has always been considered as opportunistic pathogen because it lacks obvious virulence factors. This current effort suggests that an A. caviae strain can colonize the murine intestinal tract and cause what has been described by others as a dysregulatory cytokine response. This response could explain why a number of diarrheal waterborne disease cases have been attributed to A. caviae even though it lacks obvious enteropathogenic properties.

  11. Liv. 52 protection against radiation induced lesions in mammalian liver

    International Nuclear Information System (INIS)

    Saini, M.R.; Saini, N.

    1985-01-01

    Effect of Liv. 52 on mammalian liver was studied after whole-body exposure to 5.5 Gy of 60 Co gamma radiation. It was found that the drug protected the organ against radiation-induced changes. The protective effect was manifested in the form of early recovery as indicated by the absence of pathological changes like cytoplasmic degranulation, loss of nulei from many cells and abnormal architecture at 10 days and restoration of normal structure by 4 weeks. Liv. 52 may neutralize the peroxides formed from water molecules after irradiation which are toxic and cause the damage to the organ. Thus it seems that the drug may act as detoxicating agent. (author)

  12. Mechanism for radiation-induced damage via TLR3 on the intestinal epithelium

    International Nuclear Information System (INIS)

    Takemura, Naoki; Uematsu, Satoshi

    2014-01-01

    When the small-intestinal epithelium is injured due to high-dose radiation exposure, radiation-induced gastrointestinal syndrome (GIS) such as absorption inhibition and intestinal bacterial infection occurs, and lead to subacute death. The authors immunologically analyzed the disease onset mechanism of GIS. In the small-intestinal mucosal epithelium, the intestinal epithelial stem cells of crypt structure and their daughter cells are renewed through proliferation and differentiation in the cycle of 3 or 4 days. When DNA is damaged by radiation, although p53 gene stops cell cycle and repairs DNA, cell death is induced if the repair is impossible. When stem cells perish, cell supply stops resulting in epithelial breakdown and fatal GIS. The authors analyzed the involvement in GIS of toll-like receptor (TLR) with the function of natural immunity, based on lethal γ-ray irradiation on KO mice and other methods. The authors found the mechanism, in which RNA that was leaked due to cell death caused by p53 gene elicits inflammation by activating TLR3, and leads to GIS through a wide range of cell death induction and stem cell extinction. The administration of a TLR3/RNA binding inhibitor before the irradiation of mice decreased crypt cell death and greatly improved survival rate. The administration one hour after the irradiation also showed improvement. The administration of the TLR3 specific inhibitor within a fixed time after the exposure is hopeful for the prevention of GIS, without affecting the DNA repair function of p53 gene. (A.O.)

  13. Maternal Obesity Induces Sustained Inflammation in Both Fetal and Offspring Large Intestine of Sheep

    Science.gov (United States)

    Yan, Xu; Huang, Yan; Wang, Hui; Du, Min; Hess, Bret W.; Ford, Stephen P.; Nathanielsz, Peter W.; Zhu, Mei-Jun

    2010-01-01

    Background Both maternal obesity and inflammatory bowel diseases (IBDs) are increasing. It was hypothesized that maternal obesity induces an inflammatory response in the fetal large intestine, predisposing offspring to IBDs. Methods Nonpregnant ewes were assigned to a control (Con, 100% of National Research Council [NRC] recommendations) or obesogenic (OB, 150% of NRC) diet from 60 days before conception. The large intestine was sampled from fetuses at 135 days (term 150 days) after conception and from offspring lambs at 22.5 ± 0.5 months of age. Results Maternal obesity enhanced mRNA expression tumor necrosis factor (TNF)α, interleukin (IL)1α, IL1β, IL6, IL8, and monocyte/macrophage chemotactic protein-1 (MCP1), as well as macrophage markers, CD11b, CD14, and CD68 in fetal gut. mRNA expression of Toll-like receptor (TLR) 2 and TLR4 was increased in OB versus Con fetuses; correspondingly, inflammatory NF-κB and JNK signaling pathways were also upregulated. Both mRNA expression and protein content of transforming growth factor (TGF) β was increased. The IL-17A mRNA expression and protein content was higher in OB compared to Con samples, which was associated with fibrosis in the large intestine of OB fetuses. Similar inflammatory responses and enhanced fibrosis were detected in OB compared to Con offspring. Conclusions Maternal obesity induced inflammation and enhanced expression of proinflammatory cytokines in fetal and offspring large intestine, which correlated with increased TGFβ and IL17 expression. These data show that maternal obesity may predispose offspring gut to IBDs. PMID:21674707

  14. Probiotics and Probiotic Metabolic Product Improved Intestinal Function and Ameliorated LPS-Induced Injury in Rats.

    Science.gov (United States)

    Deng, Bo; Wu, Jie; Li, Xiaohui; Men, Xiaoming; Xu, Ziwei

    2017-11-01

    In the present study, we sought to determine the effects of Bacillus subtilis (BAS) and Bacillus licheniformis (BAL) in rats after lipopolysaccharide (LPS)-induced acute intestinal inflammation. We also determined whether the B. subtilis metabolic product (BASM) is as effective as the live-cell probiotic. 60 male SD rats were randomly assigned to five groups and administered a diet containing 0.05% B. licheniformis (BAL group), 0.05% B. subtilis (BAS group), 0.5% B. subtilis metabolic product (BASM group), or a basic diet (PC group and NC group) for 40 days. On day 40, BAL, BAS, BASM, and NC groups were injected with 4 mg/kg body weight LPS. 4 h later, all rats were anesthetized and sacrificed. The results showed that the administration of B. licheniformis and B. subtilis improved intestinal function as evidenced by histology, increased enzyme activity, and mucosal thickness. They also increased the number of intraepithelial lymphocytes and decreased mucosal myeloperoxidase activity and plasma TNF-α. In addition, the cecal content of B. subtilis-treated rats had significantly increased microbial diversity, decreased numbers of Firmicutes, and increased numbers of Bacteroidetes as compared to rats fed basic diets. Similar to BAS group, the cecal content of B. licheniformis-treated rats decreased the number of Firmicutes. Administration of B. subtilis metabolic product had similar effects on intestinal function, inflammation response, and microbial diversity as B. subtilis but these effects were attenuated. In conclusion, administration of probiotic strains B. licheniformis or B. subtilis improved intestinal function, ameliorated the inflammation response, and modulated microflora after LPS-induced acute inflammation in rats. Non-living cells also exerted probiotic properties but live cells tended to function better.

  15. Traditional Herbal Medicine, Rikkunshito, Induces HSP60 and Enhances Cytoprotection of Small Intestinal Mucosal Cells as a Nontoxic Chaperone Inducer

    Directory of Open Access Journals (Sweden)

    Kumiko Tamaki

    2012-01-01

    Full Text Available Increasing incidence of small intestinal ulcers associated with nonsteroidal anti-inflammatory drugs (NSAIDs has become a topic with recent advances of endoscopic technology. However, the pathogenesis and therapy are not fully understood. The aim of this study is to examine the effect of Rikkunshito (TJ-43, a traditional herbal medicine, on expression of HSP60 and cytoprotective ability in small intestinal cell line (IEC-6. Effect of TJ-43 on HSP60 expression in IEC-6 cells was evaluated by immunoblot analysis. The effect of TJ-43 on cytoprotective abilities of IEC-6 cells against hydrogen peroxide or indomethacin was studied by MTT assay, LDH-release assay, caspase-8 activity, and TUNEL. HSP60 was significantly induced by TJ-43. Cell necrosis and apoptosis were significantly suppressed in IEC-6 cells pretreated by TJ-43 with overexpression of HSP60. Our results suggested that HSP60 induced by TJ-43 might play an important role in protecting small intestinal epithelial cells from apoptosis and necrosis in vitro.

  16. Roles of pro-angiogenic and anti-angiogenic factors as well as matrix metalloproteinases in healing of NSAID-induced small intestinal ulcers in rats.

    Science.gov (United States)

    Gyenge, Melinda; Amagase, Kikuko; Kunimi, Shino; Matsuoka, Rie; Takeuchi, Koji

    2013-10-06

    We examined changes in the expression of a pro-angiogenic factor, vascular endothelial growth factor (VEGF), and an anti-angiogenic factor, endostatin, as well as matrix metalloproteinase (MMP)-2 and MMP-9 in the rat small intestine after administration of indomethacin and investigated the roles of these factors in the healing of indomethacin-induced small intestinal ulcers. Male SD rats were given indomethacin (10mg/kg) p.o. and euthanized at various time points (3-24h and 2-7days) after the administration. To impair the healing of these lesions, low-dose of indomethacin (2mg/kg) was given p.o. once daily for 6days starting 1day after ulceration. Levels of VEGF, endostatin, MMP-2 and MMP-9 were determined by Western blotting. The expression of both VEGF and endostatin was upregulated after the ulceration. Repeated administration of low-dose indomethacin impaired the ulcer healing with a decrease of VEGF expression and a further increase of endostatin expression, resulting in a marked decrease in the ratio of VEGF/endostatin expression. The levels of MMP-2 and MMP-9 were both significantly increased after the ulceration, but these responses were suppressed by the repeated indomethacin treatment. The healing of these ulcers was significantly delayed by the repeated administration of MMP inhibitors such as ARP-101 and SB-3CT. The results confirm the importance of the balance between pro-angiogenic and anti-angiogenic activities in the healing of indomethacin-induced small intestinal damage and further suggest that the increased expression of MMP-2 and MMP-9 is another important factor for ulcer healing in the small intestine. © 2013.

  17. Increased sensitivity of DNA damage response-deficient cells to stimulated microgravity-induced DNA lesions.

    Directory of Open Access Journals (Sweden)

    Nan Li

    Full Text Available Microgravity is a major stress factor that astronauts have to face in space. In the past, the effects of microgravity on genomic DNA damage were studied, and it seems that the effect on genomic DNA depends on cell types and the length of exposure time to microgravity or simulated microgravity (SMG. In this study we used mouse embryonic stem (MES and mouse embryonic fibroblast (MEF cells to assess the effects of SMG on DNA lesions. To acquire the insight into potential mechanisms by which cells resist and/or adapt to SMG, we also included Rad9-deleted MES and Mdc1-deleted MEF cells in addition to wild type cells in this study. We observed significant SMG-induced DNA double strand breaks (DSBs in Rad9-/- MES and Mdc1-/- MEF cells but not in their corresponding wild type cells. A similar pattern of DNA single strand break or modifications was also observed in Rad9-/- MES. As the exposure to SMG was prolonged, Rad9-/- MES cells adapted to the SMG disturbance by reducing the induced DNA lesions. The induced DNA lesions in Rad9-/- MES were due to SMG-induced reactive oxygen species (ROS. Interestingly, Mdc1-/- MEF cells were only partially adapted to the SMG disturbance. That is, the induced DNA lesions were reduced over time, but did not return to the control level while ROS returned to a control level. In addition, ROS was only partially responsible for the induced DNA lesions in Mdc1-/- MEF cells. Taken together, these data suggest that SMG is a weak genomic DNA stress and can aggravate genomic instability in cells with DNA damage response (DDR defects.

  18. Development of large intestinal attaching and effacing lesions in pigs in association with the feeding of a particular diet.

    Science.gov (United States)

    Neef, N A; McOrist, S; Lysons, R J; Bland, A P; Miller, B G

    1994-10-01

    Hysterotomy-derived piglets were kept in gnotobiotic isolators and artificially colonized at 7 days of age with an adult bovine enteric microflora. At 3 weeks of age, the pigs were transferred to conventional experimental accommodation and weaned, either onto a solid diet that had been associated with field cases of typhlocolitis in pigs or onto a solid control diet. At necropsy at 5 weeks of age, groups of pigs fed the diet associated with field cases of typhlocolitis were found to have developed typhlocolitis. This was absent from the groups fed the control diet. The typhlocolitis was characterized by attaching and effacing lesions typical of those described following experimental inoculation of various species with enteropathogenic Escherichia coli. A nonverocytotoxic, eae probe-positive E. coli serotype O116 was isolated from pigs on the colitis-associated diet but not from any of the pigs on the control diet. Coliform bacteria attached to the colonic lesions reacted with polyclonal antiserum to E. coli O116 in an immunoperoxidase assay of histological sections of affected tissue. No reaction with this antiserum was observed in corresponding tissue sections taken from pigs on the control diet. No colon lesions were observed in germfree pigs fed either of the diets. It is postulated that proliferation and possibly expression of pathogenicity of the attaching and effacing E. coli responsible for the lesions are strongly influenced by diet.

  19. Murine P-glycoprotein deficiency alters intestinal injury repair and blunts lipopolysaccharide-induced radioprotection.

    Science.gov (United States)

    Staley, Elizabeth M; Yarbrough, Vanisha R; Schoeb, Trenton R; Daft, Joseph G; Tanner, Scott M; Steverson, Dennis; Lorenz, Robin G

    2012-09-01

    P-glycoprotein (P-gp) has been reported to increase stem cell proliferation and regulate apoptosis. Absence of P-gp results in decreased repair of intestinal epithelial cells after chemical injury. To further explore the mechanisms involved in the effects of P-gp on intestinal injury and repair, we used the well-characterized radiation injury model. In this model, injury repair is mediated by production of prostaglandins (PGE(2)) and lipopolysaccharide (LPS) has been shown to confer radioprotection. B6.mdr1a(-/-) mice and wild-type controls were subjected to 12 Gy total body X-ray irradiation and surviving crypts in the proximal jejunum and distal colon were evaluated 3.5 days after irradiation. B6.mdr1a(-/-) mice exhibited normal baseline stem cell proliferation and COX dependent crypt regeneration after irradiation. However, radiation induced apoptosis was increased and LPS-induced radioprotection was blunted in the C57BL6.mdr1a(-/-) distal colon, compared to B6 wild-type controls. The LPS treatment induced gene expression of the radioprotective cytokine IL-1α, in B6 wild-type controls but not in B6.mdr1a(-/-) animals. Lipopolysaccharid-induced radioprotection was absent in IL-1R1(-/-) animals, indicating a role for IL-1α in radioprotection, and demonstrating that P-gp deficiency interferes with IL-1α gene expression in response to systemic exposure to LPS.

  20. Bovine lactoferrin decreases cholera-toxin-induced intestinal fluid accumulation in mice by ganglioside interaction.

    Directory of Open Access Journals (Sweden)

    Fulton P Rivera

    Full Text Available Secretory diarrhea caused by cholera toxin (CT is initiated by binding of CT's B subunit (CTB to GM1-ganglioside on the surface of intestinal cells. Lactoferrin, a breast milk glycoprotein, has shown protective effect against several enteropathogens. The aims of this study were to determine the effect of bovine-lactoferrin (bLF on CT-induced intestinal fluid accumulation in mice, and the interaction between bLF and CT/CTB with the GM1-ganglioside receptor. Fluid accumulation induced by CT was evaluated in the mouse ileal loop model using 56 BALB/c mice, with and without bLF added before, after or at the same time of CT administration. The effect of bLF in the interaction of CT and CTB with GM1-ganglioside was evaluated by a GM1-enzyme-linked immunosorbent assay. bLF decreased CT-induced fluid accumulation in the ileal loop of mice. The greatest effect was when bLF was added before CT (median, 0.066 vs. 0.166 g/cm, with and without bLF respectively, p<0.01. We conclude that bLF decreases binding of CT and CTB to GM1-ganglioside, suggesting that bLF suppresses CT-induced fluid accumulation by blocking the binding of CTB to GM1-ganglioside. bLF may be effective as adjunctive therapy for treatment of cholera diarrhea.

  1. DNA lesions induced by replication stress trigger mitotic aberration and tetraploidy development.

    Directory of Open Access Journals (Sweden)

    Yosuke Ichijima

    Full Text Available During tumorigenesis, cells acquire immortality in association with the development of genomic instability. However, it is still elusive how genomic instability spontaneously generates during the process of tumorigenesis. Here, we show that precancerous DNA lesions induced by oncogene acceleration, which induce situations identical to the initial stages of cancer development, trigger tetraploidy/aneuploidy generation in association with mitotic aberration. Although oncogene acceleration primarily induces DNA replication stress and the resulting lesions in the S phase, these lesions are carried over into the M phase and cause cytokinesis failure and genomic instability. Unlike directly induced DNA double-strand breaks, DNA replication stress-associated lesions are cryptogenic and pass through cell-cycle checkpoints due to limited and ineffective activation of checkpoint factors. Furthermore, since damaged M-phase cells still progress in mitotic steps, these cells result in chromosomal mis-segregation, cytokinesis failure and the resulting tetraploidy generation. Thus, our results reveal a process of genomic instability generation triggered by precancerous DNA replication stress.

  2. The spatial resolution of the porcine multifocal electroretinogram for detection of laser-induced retinal lesions

    DEFF Research Database (Denmark)

    Kyhn, Maria Voss; Kiilgaard, Jens Folke; Scherfig, Erik

    2008-01-01

    This study aimed to investigate the spatial resolution of a porcine multifocal electroretinogram (mfERG) protocol by testing its ability to detect laser-induced retinal lesions. Furthermore, we wanted to describe time-dependent changes in implicit time and amplitude of the different mfERG peaks...

  3. Axonal lesion-induced microglial proliferation and microglial cluster formation in the mouse

    DEFF Research Database (Denmark)

    Dissing-Olesen, L; Ladeby, R; Nielsen, Helle Hvilsted

    2007-01-01

    Microglia are innate immune cells and form the first line of defense of the CNS. Proliferation is a key event in the activation of microglia in acute pathology, and has been extensively characterized in rats, but not in mice. In this study we investigated axonal-lesion-induced microglial prolifer...

  4. Are lesions induced by ionizing radiation direct blocks to DNA chain elongation

    International Nuclear Information System (INIS)

    Painter, R.B.

    1983-01-01

    Ionizing radiation blocks DNA chain elongation in normal diploid fibroblasts but not in fibroblasts from patients with ataxia-telangiectasia, even though there are no differences in the damage induced between the two cell types. This difference suggests that radiation-induced lesions in DNA are not themselves blocks to chain elongation in ataxia cells and raises the possibility that in normal cells a mediator exists between DNA damage and chain termination

  5. Staphylococcus aureus induces IL-8 expression through its lipoproteins in the human intestinal epithelial cell, Caco-2.

    Science.gov (United States)

    Kang, Seok-Seong; Noh, Su Young; Park, Ok-Jin; Yun, Cheol-Heui; Han, Seung Hyun

    2015-09-01

    Staphylococcus aureus can cause the intestinal inflammatory diseases. However, little is known about the molecular mechanism of S. aureus infection in the intestine. In the present study, we investigated whether S. aureus could stimulate human intestinal epithelial cells triggering inflammation. When the human intestinal epithelial cell-line, Caco-2, and the primary colon cells were stimulated with ethanol-inactivated S. aureus, IL-8 expression was induced in a dose-dependent manner. The inactivated S. aureus preferentially stimulated Toll-like receptor (TLR) 2 rather than TLR4. Lipoproteins, lipoteichoic acid (LTA), and peptidoglycan (PGN) are considered as potential TLR2 ligands of S. aureus. Interestingly, S aureus lipoproteins and Pam2CSK4 mimicking Gram-positive bacterial lipoproteins, but not LTA and PGN of S. aureus, significantly induced IL-8 expression in Caco-2 cells. Furthermore, lipoprotein-deficient S. aureus mutant strain failed to induce IL-8 production. Collectively, these results suggest that S. aureus stimulates the human intestinal epithelial cells to induce the chemokine IL-8 production through its lipoproteins, potentially contributing the development of intestinal inflammation. Copyright © 2015 Elsevier Ltd. All rights reserved.

  6. Transcriptional corepressor MTG16 regulates small intestinal crypt proliferation and crypt regeneration after radiation-induced injury.

    Science.gov (United States)

    Poindexter, Shenika V; Reddy, Vishruth K; Mittal, Mukul K; Williams, Amanda M; Washington, M Kay; Harris, Elizabeth; Mah, Amanda; Hiebert, Scott W; Singh, Kshipra; Chaturvedi, Rupesh; Wilson, Keith T; Lund, P Kay; Williams, Christopher S

    2015-03-15

    Myeloid translocation genes (MTGs) are transcriptional corepressors implicated in development, malignancy, differentiation, and stem cell function. While MTG16 loss renders mice sensitive to chemical colitis, the role of MTG16 in the small intestine is unknown. Histological examination revealed that Mtg16(-/-) mice have increased enterocyte proliferation and goblet cell deficiency. After exposure to radiation, Mtg16(-/-) mice exhibited increased crypt viability and decreased apoptosis compared with wild-type (WT) mice. Flow cytometric and immunofluorescence analysis of intestinal epithelial cells for phospho-histone H2A.X also indicated decreased DNA damage and apoptosis in Mtg16(-/-) intestines. To determine if Mtg16 deletion affected epithelial cells in a cell-autonomous fashion, intestinal crypts were isolated from Mtg16(-/-) mice. Mtg16(-/-) and WT intestinal crypts showed similar enterosphere forming efficiencies when cultured in the presence of EGF, Noggin, and R-spondin. However, when Mtg16(-/-) crypts were cultured in the presence of Wnt3a, they demonstrated higher enterosphere forming efficiencies and delayed progression to mature enteroids. Mtg16(-/-) intestinal crypts isolated from irradiated mice exhibited increased survival compared with WT intestinal crypts. Interestingly, Mtg16 expression was reduced in a stem cell-enriched population at the time of crypt regeneration. This is consistent with MTG16 negatively regulating regeneration in vivo. Taken together, our data demonstrate that MTG16 loss promotes radioresistance and impacts intestinal stem cell function, possibly due to shifting cellular response away from DNA damage-induced apoptosis and towards DNA repair after injury.

  7. Ageing sensitized by iPLA2β deficiency induces liver fibrosis and intestinal atrophy involving suppression of homeostatic genes and alteration of intestinal lipids and bile acids.

    Science.gov (United States)

    Jiao, Li; Gan-Schreier, Hongying; Zhu, Xingya; Wei, Wang; Tuma-Kellner, Sabine; Liebisch, Gerhard; Stremmel, Wolfgang; Chamulitrat, Walee

    2017-12-01

    Ageing is a major risk factor for various forms of liver and gastrointestinal (GI) disease and genetic background may contribute to the pathogenesis of these diseases. Group VIA phospholipase A2 or iPLA 2 β is a homeostatic PLA 2 by playing a role in phospholipid metabolism and remodeling. Global iPLA 2 β -/- mice exhibit aged-dependent phenotypes with body weight loss and abnormalities in the bone and brain. We have previously reported the abnormalities in these mutant mice showing susceptibility for chemical-induced liver injury and colitis. We hypothesize that iPLA 2 β deficiency may sensitize with ageing for an induction of GI injury. Male wild-type and iPLA 2 β -/- mice at 4 and 20-22months of age were studied. Aged, but not young, iPLA 2 β -/- mice showed increased hepatic fibrosis and biliary ductular expansion as well as severe intestinal atrophy associated with increased apoptosis, pro-inflammation, disrupted tight junction, and reduced number of mucin-containing globlet cells. This damage was associated with decreased expression of intestinal endoplasmic stress XBP1 and its regulator HNF1α, FATP4, ACSL5, bile-acid transport genes as well as nuclear receptors LXRα and FXR. By LC/MS-MS profiling, iPLA 2 β deficiency in aged mice caused an increase of intestinal arachidonate-containing phospholipids concomitant with a decrease in ceramides. By the suppression of intestinal FXR/FGF-15 signaling, hepatic bile-acid synthesis gene expression was increased leading to an elevation of secondary and hydrophobic bile acids in liver, bile, and intestine. In conclusions, ageing sensitized by iPLA 2 β deficiency caused a decline of key intestinal homeostatic genes resulting in the development of GI disease in a gut-to-liver manner. Copyright © 2017 Elsevier B.V. All rights reserved.

  8. Vinorelbine induced perforation of a metastatic gastric lesion.

    Science.gov (United States)

    Mullally, W J; O'Súilleabháin, C B; Brady, C; O'Reilly, S

    2017-08-01

    Breast carcinoma metastasis to the gastrointestinal tract is rare and more frequently associated with lobular than ductal carcinoma (Borst and Ingold, Surg 114(4):637-641 [1]). The purpose of this article is to present a case based review of a unique gastrointestinal metastasis and literature review. A 46 year old lady with metastatic invasive ductal breast cancer was admitted to A&E with sudden onset of epigastric and left shoulder pain. She completed the first cycle of capecitabine/vinorelbine 1 week previously. Clinical examination revealed a tender epigastrium with rigidity in the upper abdomen. Free air under the diaphragm and a positive Rigler's sign was radiologically identified. A laparoscopy demonstrated a fibrinous exudate in the left upper quadrant consistent with a walled off lesser curvature gastric perforation. A subsequent oesophagogastroduodenoscopy (OGD) demonstrated a healed gastric ulcer of benign appearance; however the pathology confirmed metastatic breast carcinoma. Literature review confirmed no previously reported cases of vinorelbine induced gastric perforation. Four cases of metastatic breast cancer with gastric metastasis presenting with perforation were identified; three of these cases (Fra et al., Presse Med 25(26):1215 (1996) [2], Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3], Ghosn et al., Bull Cancer 78(11):1071-1073 (1991) [4]), were in the French medical literature, including one male patient (Fra et al., Presse Med 25(26):1215 (1996) [2]) and at least one ductal breast carcinoma (Solis-Caxaj et al., Gastroenterol Clin Biol 28(1):91-92 (2004) [3]). The fourth case (van Geel et al., Ned Tijdschr Geneeskd 144(37):1761-1763 (2000) [5]), was in the Dutch medical literature and a lobular breast carcinoma. This case represents a rare complication of breast cancer chemotherapy, the subsequent significant benefit the patient received from treatment is consistent with the chemosensitivity to therapy that also resulted

  9. Lesions induced in rodent pancreas by azaserine and other pancreatic carcinogens

    Energy Technology Data Exchange (ETDEWEB)

    Longnecker, D.S.

    1984-06-01

    Focal proliferative changes in the acinar cells of the pancreas of rats have been induced by several systemically administered carcinogens including azaserine, N-nitrosobis(2-oxopropyl)amine, N-nitroso(2-hydroxypropyl) (2-oxopropyl)amine, and Ndelta-(N-methyl-N-nitrosocarbamoyl)-L-ornithine (MNCO). Foci, nodules, and adenomas induced by these carcinogens are usually made up of atypical-appearing acinar cells that maintain a high degree of differentiation, but a minority of these lesions exhibit anaplastic cellular changes that suggest the development of malignant potential. Such anaplasia may occupy the whole of smaller lesions or may occur as a secondary focal change within larger nodules or adenomas. Many foci and nodules per pancreas have been induced by single or multiple exposures to these known genotoxic carcinogens, but relatively few of them develop into carcinomas. Azaserine and MNCO have induced acinar cell carcinomas in rats. Those induced by azaserine have exhibited a broad spectrum of histologic variants, including ductlike, cystic and undifferentiated patterns. Higher doses of MNCO have induced a second pattern of change in the pancreatic lobules of rats, which includes cystic and tubular ductlike structures that have been called cystic and tubular ductal complexes. MNCO has also induced focal acinar cell lesions, cystic and tubular ductal complexes, and adenocarcinomas in the pancreas of Syrian golden hamsters. In this species, ductal complexes are much more numerous than are proliferative lesions of acinar cells, and the histologic appearance of the carcinomas is ductlike. Hyperplasia and atypical changes were also seen in the epithelium of the intralobular ducts of hamsters. 20 references, 5 figures, 1 table.

  10. Effects of Saccharomyces cerevisiae or boulardii yeasts on acute stress induced intestinal dysmotility.

    Science.gov (United States)

    West, Christine; Stanisz, Andrew M; Wong, Annette; Kunze, Wolfgang A

    2016-12-28

    To investigate the capacity of Saccharomyces cerevisiae ( S. cerevisiae ) and Saccharomyces boulardii ( S. boulardii ) yeasts to reverse or to treat acute stress-related intestinal dysmotility. Adult Swiss Webster mice were stressed for 1 h in a wire-mesh restraint to induce symptoms of intestinal dysmotility and were subsequently killed by cervical dislocation. Jejunal and colon tissue were excised and placed within a tissue perfusion bath in which S. cerevisiae , S. boulardii , or their supernatants were administered into the lumen. Video recordings of contractility and gut diameter changes were converted to spatiotemporal maps and the velocity, frequency, and amplitude of propagating contractile clusters (PCC) were measured. Motility pre- and post-treatment was compared between stressed animals and unstressed controls. S. boulardii and S. cerevisiae helped to mediate the effects of stress on the small and large intestine. Restraint stress reduced jejunal transit velocity (mm/s) from 2.635 ± 0.316 to 1.644 ± 0.238, P boulardii helped to restore jejunal and colonic velocity towards the unstressed controls; 1.833 ± 0.688 to 2.627 ± 0.664, P boulardii or S. cerevisiae supernatants also helped to restore motility to unstressed values in similar capacity. There is a potential therapeutic role for S. cerevisiae and S. boulardii yeasts and their supernatants in the treatment of acute stress-related gut dysmotility.

  11. Diet-Induced Dysbiosis of the Intestinal Microbiota and the Effects on Immunity and Disease

    Directory of Open Access Journals (Sweden)

    Deanna L. Gibson

    2012-08-01

    Full Text Available The gastrointestinal (GI microbiota is the collection of microbes which reside in the GI tract and represents the largest source of non-self antigens in the human body. The GI tract functions as a major immunological organ as it must maintain tolerance to commensal and dietary antigens while remaining responsive to pathogenic stimuli. If this balance is disrupted, inappropriate inflammatory processes can result, leading to host cell damage and/or autoimmunity. Evidence suggests that the composition of the intestinal microbiota can influence susceptibility to chronic disease of the intestinal tract including ulcerative colitis, Crohn’s disease, celiac disease and irritable bowel syndrome, as well as more systemic diseases such as obesity, type 1 diabetes and type 2 diabetes. Interestingly, a considerable shift in diet has coincided with increased incidence of many of these inflammatory diseases. It was originally believed that the composition of the intestinal microbiota was relatively stable from early childhood; however, recent evidence suggests that diet can cause dysbiosis, an alteration in the composition of the microbiota, which could lead to aberrant immune responses. The role of the microbiota and the potential for diet-induced dysbiosis in inflammatory conditions of the GI tract and systemic diseases will be discussed.

  12. Intestinal Lesion in a Dog Due to Cryptococcus gattii Type VGII and Review of Published Cases of Canine Gastrointestinal Cryptococcosis.

    Science.gov (United States)

    de Abreu, Daniel Paiva Barros; Machado, Carlos Henrique; Makita, Mário Tatsuo; Botelho, Camila Flávia Magalhães; Oliveira, Fernanda Gomes; da Veiga, Cristiano Chaves Pessoa; Martins, Marilena Dos Anjos; Baroni, Francisco de Assis

    2017-06-01

    Cryptococcosis is a mycosis caused by yeasts of genus Cryptococcus, mainly the species C. neoformans and C. gattii that can affect humans and animals. These yeasts are widely distributed in the environment and are typically associated with avian droppings and decaying wood. Most infections are related to the respiratory tract, but the central nervous system and cutaneous lesions are also reported in the literature. The present report is a case of cryptococcosis in an 18-month-old unspayed female English Bulldog with the main complaint of weight loss and diarrhea. The presence of two large masses observed in an ultrasound examination leads us to perform an exploratory laparotomy. Considering the size of the lesion and the impossibility of owner to provide intensive care, the consent for euthanasia was requested. The postmortem diagnosis of cryptococcosis was revealed by cytological evaluation, and the involvement of C. gattii VGII was confirmed by isolation and identification tests as well as by the detection of the URA5 gene restriction fragment length polymorphism PCR analysis. Reports in the literature of the involvement of Cryptococcus in gastrointestinal lesions are rare in both human and veterinary medicine. Data about different forms of cryptococcosis are important to provide more knowledge of uncommon clinical presentations of this yeast and therefore improve the diagnoses and decisions for the best therapy.

  13. Combined compared to dissociated oral and intestinal sucrose stimuli induce different brain hedonic processes

    Directory of Open Access Journals (Sweden)

    Caroline eClouard

    2014-08-01

    Full Text Available The characterization of brain networks contributing to the processing of oral and/or intestinal sugar signals in a relevant animal model might help to understand the neural mechanisms related to the control of food intake in humans and suggest potential causes for impaired eating behaviors. This study aimed at comparing the brain responses triggered by oral and/or intestinal sucrose sensing in pigs. Seven animals underwent brain single photon emission computed tomography (99mTc-HMPAO further to oral stimulation with neutral or sucrose artificial saliva paired with saline or sucrose infusion in the duodenum, the proximal part of the intestine. Oral and/or duodenal sucrose sensing induced differential cerebral blood flow (CBF changes in brain regions known to be involved in memory, reward processes and hedonic (i.e. pleasure evaluation of sensory stimuli, including the dorsal striatum, prefrontal cortex, cingulate cortex, insular cortex, hippocampus and parahippocampal cortex. Sucrose duodenal infusion only and combined sucrose stimulation induced similar activity patterns in the putamen, ventral anterior cingulate cortex and hippocampus. Some brain deactivations in the prefrontal and insular cortices were only detected in the presence of oral sucrose stimulation. Finally, activation of the right insular cortex was only induced by combined oral and duodenal sucrose stimulation, while specific activity patterns were detected in the hippocampus and parahippocampal cortex with oral sucrose dissociated from caloric load. This study sheds new light on the brain hedonic responses to sugar and has potential implications to unravel the neuropsychological mechanisms underlying food pleasure and motivation.

  14. Differences in the location and activity of intestinal Crohn's disease lesions between adult and paediatric patients detected with MRI

    Energy Technology Data Exchange (ETDEWEB)

    Maccioni, Francesca; Carrozzo, Federica; Pino, Anna Rosaria; Staltari, Ilaria; Ansari, Najwa Al; Marini, Mario [Rome University, Department of Radiological Sciences, Oncology and Pathology, Policlinico Umberto I Hospital, Rome (Italy); Viola, Franca; Di Nardo, Giovanni; Cucchiara, Salvatore [Rome University, Department of Pediatrics, Pediatric Gastroenterology and Liver Unit Policlinico Umberto I Hospital, Rome (Italy); Vestri, Annarita [Rome University, Department of Statistical Sciences, Policlinico Umberto I Hospital, Roma (Italy); Signore, Alberto [Rome University, Nuclear Medicine Unit, Faculty Medicine and Psychology, 2nd Faculty of Medicine, S. Andrea Hospital, Rome (Italy)

    2012-11-15

    To prospectively compare paediatric patients (PP) and adult patients (AP) affected by Crohn's disease (CD) in terms of the location and activity of intestinal lesions. Forty-three children (mean age 15 years) and 43 adults (mean age 48 years) with proven CD underwent magnetic resonance enterography (MRE) to localise lesions and detect their activity in 9 segments of the small and large bowel. The results were analysed on a per patient and per segment basis. Ileo-colonoscopy was performed in all patients. P values less than 0.05 were considered statistically significant. Involvement of terminal ileum was significantly different in the two groups: observed in 100 % of AP (43/43) versus 58 % (23/43) of PP (P < 0.0001). Conversely, the colon was diseased in 84 % of PP versus 64 % of AP. In particular, left colonic segments were significantly more involved in PP (descending colon 53 % versus 21 %, P < 0.01; rectum 67 % versus 23 %, P < 0.0001; sigmoid colon 56 % versus 37 %, not significant), whereas caecal involvement was equal in both groups. In children the maximal disease activity was found in left colonic segments, whereas in adults it was in the terminal ileum. MRE detected significant differences between the two populations, showing a more extensive and severe involvement of the left colon in children but the distal ileum in adults. (orig.)

  15. In vitro enzymatic studies on the nature and repair of x-ray induced lesions in DNA

    International Nuclear Information System (INIS)

    Wallace, S.S.

    1979-01-01

    Areas studied include: purification and properties of enzyme probes for x-ray induced DNA lesions using E. Coli x-ray endonuclease and S. cerevisiae endonuclease E; use of enzymes probes; and use of physical, chemical and enzymatic probes to quantify x-ray-induced lesions in viruses and cells

  16. Influence of caffeine on chromosome lesions induced by chemical mutagens and radiation. 2

    International Nuclear Information System (INIS)

    Dimitrov, B.

    1977-01-01

    The modifying influence of caffeine on γ-ray induced chromosome lesions was studied by chromosome aberration anaysis. Caffeine was applied as a pre- and post-treatment agent following seed (G 1 ) and root meristem (G 2 and S) irradiation of C.capillaris. The frequency of chromosome aberrations induced in G 1 was changed neither by post- nor by pre-treatment with caffeine. This fact proves the lack of caffeine modifying effect. Applied as a post-treatment agent caffeine enhances considerably the frequency of chromosome aberrations induced in root meristem cells. This is especially valid for G 2 irradiated cells, while in S cells no synergistic effect was established between induced chromosome lesions and caffeine. The enhancement of chromosome aberration frequency produced in G 2 shows a clearly manifested dependence on the time (moment) of caffeine application post irradiation. Most considerable enhancement was obtained following post-treatment with caffeine immediately after irradiation. In the following intervals - 15 and 30 min - it decreases progressively, while after 60, 180 and 300 min no enhancing effect is observed. The probable causes for the manifestation and the lack of synergistic effect between chromosome lesions induced in the various mitotic cycle phases and caffeine are discussed. (author)

  17. Functional remineralization of dentin lesions using polymer-induced liquid-precursor process.

    Directory of Open Access Journals (Sweden)

    Anora K Burwell

    Full Text Available It was hypothesized that applying the polymer-induced liquid-precursor (PILP system to artificial lesions would result in time-dependent functional remineralization of carious dentin lesions that restores the mechanical properties of demineralized dentin matrix. 140 µm deep artificial caries lesions were remineralized via the PILP process for 7-28 days at 37°C to determine temporal remineralization characteristics. Poly-L-aspartic acid (27 KDa was used as the polymeric process-directing agent and was added to the remineralization solution at a calcium-to-phosphate ratio of 2.14 (mol/mol. Nanomechanical properties of hydrated artificial lesions had a low reduced elastic modulus (E(R = 0.2 GPa region extending about 70 μm into the lesion, with a sloped region to about 140 μm where values reached normal dentin (18-20 GPa. After 7 days specimens recovered mechanical properties in the sloped region by 51% compared to the artificial lesion. Between 7-14 days, recovery of the outer portion of the lesion continued to a level of about 10 GPa with 74% improvement. 28 days of PILP mineralization resulted in 91% improvement of E(R compared to the artificial lesion. These differences were statistically significant as determined from change-point diagrams. Mineral profiles determined by micro x-ray computed tomography were shallower than those determined by nanoindentation, and showed similar changes over time, but full mineral recovery occurred after 14 days in both the outer and sloped portions of the lesion. Scanning electron microscopy and energy dispersive x-ray analysis showed similar morphologies that were distinct from normal dentin with a clear line of demarcation between the outer and sloped portions of the lesion. Transmission electron microscopy and selected area electron diffraction showed that the starting lesions contained some residual mineral in the outer portions, which exhibited poor crystallinity. During remineralization

  18. Endotoxin induced chorioamnionitis prevents intestinal development during gestation in fetal sheep.

    Directory of Open Access Journals (Sweden)

    Tim G A M Wolfs

    Full Text Available Chorioamnionitis is the most significant source of prenatal inflammation and preterm delivery. Prematurity and prenatal inflammation are associated with compromised postnatal developmental outcomes, of the intestinal immune defence, gut barrier function and the vascular system. We developed a sheep model to study how the antenatal development of the gut was affected by gestation and/or by endotoxin induced chorioamnionitis.Chorioamnionitis was induced at different gestational ages (GA. Animals were sacrificed at low GA after 2d or 14d exposure to chorioamnionitis. Long term effects of 30d exposure to chorioamnionitis were studied in near term animals after induction of chorioamnionitis. The cellular distribution of tight junction protein ZO-1 was shown to be underdeveloped at low GA whereas endotoxin induced chorioamnionitis prevented the maturation of tight junctions during later gestation. Endotoxin induced chorioamnionitis did not induce an early (2d inflammatory response in the gut in preterm animals. However, 14d after endotoxin administration preterm animals had increased numbers of T-lymphocytes, myeloperoxidase-positive cells and gammadelta T-cells which lasted till 30d after induction of chorioamnionitis in then near term animals. At early GA, low intestinal TLR-4 and MD-2 mRNA levels were detected which were further down regulated during endotoxin-induced chorioamnionitis. Predisposition to organ injury by ischemia was assessed by the vascular function of third-generation mesenteric arteries. Endotoxin-exposed animals of low GA had increased contractile response to the thromboxane A2 mimetic U46619 and reduced endothelium-dependent relaxation in responses to acetylcholine. The administration of a nitric oxide (NO donor completely restored endothelial dysfunction suggesting reduced NO bioavailability which was not due to low expression of endothelial nitric oxide synthase.Our results indicate that the distribution of the tight

  19. The influence of septal lesions on sodium and water retention induced by Walker 256 tumor

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    F. Guimarães

    1999-03-01

    Full Text Available In the course of studies on the effects of septal area lesions on neuroimmunomodulation and Walker 256 tumor development, it was observed that tumor-induced sodium and water retention was less marked in lesioned than in non-lesioned rats. In the present study possible mechanisms involved in this phenomenon were investigated. The experiments were performed in septal-lesioned (LW; N = 15 and sham-operated (SW; N = 7 8-week-old male Wistar rats, which received multifocal simultaneous subcutaneous (sc inoculations of Walker 256 tumor cells about 30 days after the stereotaxic surgery. Control groups (no tumor, sham-operated food-restricted (SFR, N = 7 and lesioned food-restricted (LFR, N = 10 were subjected to a feeding pattern similar to that observed in tumor-bearing animals. Multifocal inoculation of Walker 256 tumor rapidly induces anorexia, which is paradoxically accompanied by an increase in body weight, as a result of renal Na+ and fluid retention. These effects of the tumor were also seen in LW rats, although the rise in fractional sodium balance during the early clinical period was significantly smaller than in SW rats (day 4: SW = 47.6 ± 6.4% and LW = 13.8 ± 5.2%; day 5: SW = 57.5 ± 3.5% and LW = 25.7 ± 4.8%; day 6: SW = 54.4 ± 3.8% and LW = 32.1 ± 4.4%; P<0.05, suggesting a temporary reduction in tumor-induced sodium retention. In contrast, urine output was significantly reduced in SW rats and increased in LW rats (LW up to -0.85 and SW up to 4.5 ml/100 g body weight, with no change in osmolar excretion. These temporary changes in the tumor's effects on LW rats may reflect a "reversal" of the secondary central antidiuretic response induced by the tumor (from antidiuretic to diuretic.

  20. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

    Science.gov (United States)

    Kawahara, Tomohiro; Makizaki, Yutaka; Oikawa, Yosuke; Tanaka, Yoshiki; Maeda, Ayako; Shimakawa, Masaki; Komoto, Satoshi; Moriguchi, Kyoko; Ohno, Hiroshi; Taniguchi, Koki

    2017-01-01

    Human rotavirus (RV) infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1), which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in mice administered

  1. Oral administration of Bifidobacterium bifidum G9-1 alleviates rotavirus gastroenteritis through regulation of intestinal homeostasis by inducing mucosal protective factors.

    Directory of Open Access Journals (Sweden)

    Tomohiro Kawahara

    Full Text Available Human rotavirus (RV infection is a leading cause of dehydrating diarrhea in infants and young children worldwide. Since therapeutic approaches to RV gastroenteritis are limited to alleviation of dehydration with oral rehydration solutions, more direct approaches to palliate symptoms of RV gastroenteritis are required. Treatments with probiotics have been increasingly recognized as alternative safe and low cost treatments for moderate infectious diarrhea. In this study, Bifidobacterium bifidum G9-1 (BBG9-1, which has been used as an intestinal drug for several decades, was shown to have a remarkable protective effect against RV gastroenteritis in a suckling mice model. As well as prophylactic oral administration of BBG9-1 from 2 days before RV infection, therapeutic oral administration of BBG9-1 from 1 day after RV infection significantly alleviated RV-induced diarrhea. Therapeutic administration of BBG9-1 reduced various types of damage in the small intestine, such as epithelial vacuolization and villous shortening, and significantly diminished the infectious RV titer in mixtures of cecal contents and feces. It was also shown that therapeutic administration of BBG9-1 significantly increased the number of acidic mucin-positive goblet cells and the gene expression of mucosal protective factors including MUC2, MUC3, MUC4, TGFβ1 and TFF3 in the small intestine. This led to alleviation of low gut permeability shown as decreased gene expression levels of occludin, claudin-1 and villin-1 after RV infection. Furthermore, in the small intestine, therapeutic administration of BBG9-1 significantly palliated the decreased gene expression of SGLT-1, which plays an important role in water absorption. In the large intestine, administered BBG9-1 was shown to replicate to assimilate undigested nutrients, resulting in normalization of the abnormally high osmotic pressure. These results suggested that water malabsorption caused by RV infection was alleviated in

  2. Severe Burn-Induced Intestinal Epithelial Barrier Dysfunction Is Associated With Endoplasmic Reticulum Stress and Autophagy in Mice

    Science.gov (United States)

    Huang, Yalan; Feng, Yanhai; Wang, Yu; Wang, Pei; Wang, Fengjun; Ren, Hui

    2018-01-01

    The disruption of intestinal barrier plays a vital role in the pathophysiological changes after severe burn injury, however, the underlying mechanisms are poorly understood. Severe burn causes the disruption of intestinal tight junction (TJ) barrier. Previous studies have shown that endoplasmic reticulum (ER) stress and autophagy are closely associated with the impairment of intestinal mucosa. Thus, we hypothesize that ER stress and autophagy are likely involved in burn injury-induced intestinal epithelial barrier dysfunction. Mice received a 30% total body surface area (TBSA) full-thickness burn, and were sacrificed at 0, 1, 2, 6, 12 and 24 h postburn. The results showed that intestinal permeability was increased significantly after burn injury, accompanied by the damage of mucosa and the alteration of TJ proteins. Severe burn induced ER stress, as indicated by increased intraluminal chaperone binding protein (BIP), CCAAT/enhancer-binding protein homologous protein (CHOP) and inositol-requiring enzyme 1(IRE1)/X-box binding protein 1 splicing (XBP1). Autophagy was activated after burn injury, as evidenced by the increase of autophagy related protein 5 (ATG5), Beclin 1 and LC3II/LC3I ratio and the decrease of p62. Besides, the number of autophagosomes was also increased after burn injury. The levels of p-PI3K(Ser191), p-PI3K(Ser262), p-AKT(Ser473), and p-mTOR were decreased postburn, suggesting that autophagy-related PI3K/AKT/mTOR pathway is involved in the intestinal epithelial barrier dysfunction following severe burn. In summary, severe burn injury induces the ER stress and autophagy in intestinal epithelia, leading to the disruption of intestinal barrier. PMID:29740349

  3. In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells.

    Science.gov (United States)

    Jung, Kwang Bo; Lee, Hana; Son, Ye Seul; Lee, Ji Hye; Cho, Hyun-Soo; Lee, Mi-Ok; Oh, Jung-Hwa; Lee, Jaemin; Kim, Seokho; Jung, Cho-Rok; Kim, Janghwan; Son, Mi-Young

    2018-01-01

    Human intestinal organoids (hIOs) derived from human pluripotent stem cells (hPSCs) have immense potential as a source of intestines. Therefore, an efficient system is needed for visualizing the stage of intestinal differentiation and further identifying hIOs derived from hPSCs. Here, 2 fluorescent biosensors were developed based on human induced pluripotent stem cell (hiPSC) lines that stably expressed fluorescent reporters driven by intestine-specific gene promoters Krüppel-like factor 5 monomeric Cherry (KLF5 mCherry ) and intestine-specific homeobox enhanced green fluorescence protein (ISX eGFP ). Then hIOs were efficiently induced from those transgenic hiPSC lines in which mCherry- or eGFP-expressing cells, which appeared during differentiation, could be identified in intact living cells in real time. Reporter gene expression had no adverse effects on differentiation into hIOs and proliferation. Using our reporter system to screen for hIO differentiation factors, we identified DMH1 as an efficient substitute for Noggin. Transplanted hIOs under the kidney capsule were tracked with fluorescence imaging (FLI) and confirmed histologically. After orthotopic transplantation, the localization of the hIOs in the small intestine could be accurately visualized using FLI. Our study establishes a selective system for monitoring the in vitro differentiation and for tracking the in vivo localization of hIOs and contributes to further improvement of cell-based therapies and preclinical screenings in the intestinal field.-Jung, K. B., Lee, H., Son, Y. S., Lee, J. H., Cho, H.-S., Lee, M.-O., Oh, J.-H., Lee, J., Kim, S., Jung, C.-R., Kim, J., Son, M.-Y. In vitro and in vivo imaging and tracking of intestinal organoids from human induced pluripotent stem cells. © FASEB.

  4. Protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury

    International Nuclear Information System (INIS)

    Shi, Jing; Wang, Lan; Lu, Yan; Ji, Yue; Wang, Yaqing; Dong, Ke; Kong, Xiangqing; Sun, Wei

    2017-01-01

    Radiation-induced gastrointestinal syndrome, including nausea, diarrhea and dehydration, contributes to morbidity and mortality after medical or industrial radiation exposure. No safe and effective radiation countermeasure has been approved for clinical therapy. In this study, we aimed to investigate the potential protective effects of seabuckthorn pulp and seed oils against radiation-induced acute intestinal injury. C57/BL6 mice were orally administered seabuckthorn pulp oil, seed oil and control olive oil once per day for 7 days before exposure to total-body X-ray irradiation of 7.5 Gy. Terminal deoxynucleotidyl transferase dUTP nick end labeling, quantitative real-time polymerase chain reaction and western blotting were used for the measurement of apoptotic cells and proteins, inflammation factors and mitogen-activated protein (MAP) kinases. Seabuckthorn oil pretreatment increased the post-radiation survival rate and reduced the damage area of the small intestine villi. Both the pulp and seed oil treatment significantly decreased the apoptotic cell numbers and cleaved caspase 3 expression. Seabuckthorn oil downregulated the mRNA level of inflammatory factors, including tumor necrosis factor-α, interleukin (IL)-1β, IL-6 and IL-8. Both the pulp and seed oils elevated the level of phosphorylated extracellular-signal-regulated kinase and reduced the levels of phosphorylated c-Jun N-terminal kinase and p38. Palmitoleic acid (PLA) and alpha linolenic acid (ALA) are the predominant components of pulp oil and seed oil, respectively. Pretreatment with PLA and ALA increased the post-radiation survival time. In conclusion, seabuckthorn pulp and seed oils protect against mouse intestinal injury from high-dose radiation by reducing cell apoptosis and inflammation. ALA and PLA are promising natural radiation countermeasure candidates.

  5. Celiac anti-type 2 transglutaminase antibodies induce phosphoproteome modification in intestinal epithelial Caco-2 cells.

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    Gaetana Paolella

    Full Text Available BACKGROUND: Celiac disease is an inflammatory condition of the small intestine that affects genetically predisposed individuals after dietary wheat gliadin ingestion. Type 2-transglutaminase (TG2 activity seems to be responsible for a strong autoimmune response in celiac disease, TG2 being the main autoantigen. Several studies support the concept that celiac anti-TG2 antibodies may contribute to disease pathogenesis. Our recent findings on the ability of anti-TG2 antibodies to induce a rapid intracellular mobilization of calcium ions, as well as extracellular signal-regulated kinase phosphorylation, suggest that they potentially act as signaling molecules. In line with this concept, we have investigated whether anti-TG2 antibodies can induce phosphoproteome modification in an intestinal epithelial cell line. METHODS AND PRINCIPAL FINDINGS: We studied phosphoproteome modification in Caco-2 cells treated with recombinant celiac anti-TG2 antibodies. We performed a two-dimensional electrophoresis followed by specific staining of phosphoproteins and mass spectrometry analysis of differentially phosphorylated proteins. Of 14 identified proteins (excluding two uncharacterized proteins, three were hypophosphorylated and nine were hyperphosphorylated. Bioinformatics analyses confirmed the presence of phosphorylation sites in all the identified proteins and highlighted their involvement in several fundamental biological processes, such as cell cycle progression, cell stress response, cytoskeletal organization and apoptosis. CONCLUSIONS: Identification of differentially phosphorylated proteins downstream of TG2-antibody stimulation suggests that in Caco-2 cells these antibodies perturb cell homeostasis by behaving as signaling molecules. We hypothesize that anti-TG2 autoantibodies may destabilize the integrity of the intestinal mucosa in celiac individuals, thus contributing to celiac disease establishment and progression. Since several proteins here

  6. [Myosin B ATPase activity of the intestinal smooth muscle in intestinal obstruction].

    Science.gov (United States)

    Takamatsu, H

    1983-06-01

    Intestinal smooth myosin B was prepared from muscle layers around the lesion in dogs with experimental colonic stenosis and in patients with congenital intestinal obstruction. Mg2+-ATPase activity of the myosin B was compared between the proximal dilated segment and distal segment to obstruction. Experimental colonic stenosis: In early period after surgery, proximal colons showed higher activity of myosin B ATPase than distal colons, decreasing to less than distal colon as time passed. Congenital intestinal obstruction: In three cases, whose atresia might have occurred at earlier period of gestation, proximal bowels showed less activity of myosin B ATPase than distal bowels. However, in two cases, whose atresia might have occurred at later period of gestation, and two cases with intestinal stenosis, proximal bowels indicated higher activity of myosin B ATPase than distal bowels. These data suggested that the contractibility of the proximal intestine was depending on the duration of obstruction, and it was depressed in the former patients and was accelerated in the latter patients. These results suggested that the extensive resection of dilated proximal bowel in the congenital atresia is not always necessary to obtain good postoperative intestinal dynamics at the operation of the atresial lesions which may be induced at later period of gestation. They also suggested that surgery for intestinal obstruction should be performed before the depression of intestinal contractibility to get good bowel function.

  7. Experimental nickel-induced pulmonary lesions in nonhuman primates: Histologic and ultrastructural analysis

    International Nuclear Information System (INIS)

    Haley, P.J.; Bice, D.E.; Muggenburg, B.A.; Hahn, F.F.

    1988-01-01

    The histologic and ultrastructural alterations of lung were evaluated in cynomolgus monkeys instilled with nickel subsulfide (Ni 3 S 2 ) at a final dose of 0.06 μmol/g lung with and without repeated intrapulmonary exposure to sheep red blood cells (SRBC). individual lung lobes were exposed to nickel alone, SRBC alone, or nickel and SRBC together. Lesions were found in nickel-exposed lobes only, regardless of exposure to SRBC. Lesions were more developed at 14 days than at 21 days after exposure to nickel, and were characterized by multifocal perivascular and peribronchiolar lymphocytic infiltrates along with microgranuloma formation, occasional fibrosis and moderate type II epithelial cell hyperplasia. Microgranulomas consisted of either central histiocytic cores surrounded by lymphocytic mantles or dense aggregates of epithelioid cells forming irregular interstitial nodules. Tracheobronchial lymph nodes had marked reactive hyperplasia of cortical and paracortical zones. Ultrastructural analysis of lung lesions revealed numerous well-differentiated lymphocytes intermixed with macrophages, in a background of mature collagen bundles. Cell associated particles were evaluated by energy dispersive microanalysis and found to consist of nickel and sulfur. These lesions appeared to be distinct from pneumoconiotic lesions induced by inert dusts and had histologic qualities compatible with immune-mediated phenomena. Because nickel compounds stimulate strong humoral and cellular immune responses in man, we conclude that pulmonary exposure of nonhuman primates to nickel compounds may provide information useful in delineating Immune mediated pulmonary disorders of man. (author)

  8. Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

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    C.V. Araújo

    2015-06-01

    Full Text Available Apolipoprotein E (APOE=gene, apoE=protein is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE-/- and wild-type (APOE+/+ C57BL6J male and female mice (N=86 were given either Ala-Gln (100 mM or phosphate buffered saline (PBS by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU challenge (450 mg/kg, via intraperitoneal injection. Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1 and B-cell lymphoma 2 (Bcl-2 intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001 in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05 were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE-/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE+/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE-/--challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge.

  9. Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

    International Nuclear Information System (INIS)

    Araújo, C.V.; Lazzarotto, C.R.; Aquino, C.C.; Figueiredo, I.L.; Costa, T.B.; Oliveira Alves, L.A. de; Ribeiro, R.A.; Bertolini, L.R.; Lima, A.A.M.; Brito, G.A.C.; Oriá, R.B.

    2015-01-01

    Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE -/- ) and wild-type (APOE +/+ ) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE -/- mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE +/+ mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE -/- -challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU challenge

  10. Alanyl-glutamine attenuates 5-fluorouracil-induced intestinal mucositis in apolipoprotein E-deficient mice

    Energy Technology Data Exchange (ETDEWEB)

    Araújo, C.V. [Laboratório da Biologia da Cicatrização, Ontogenia e Nutrição de Tecidos, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Lazzarotto, C.R. [Laboratório de Biologia Molecular e do Desenvolvimento, Universidade de Fortaleza, Fortaleza, CE (Brazil); Aquino, C.C.; Figueiredo, I.L.; Costa, T.B.; Oliveira Alves, L.A. de [Laboratório da Biologia da Cicatrização, Ontogenia e Nutrição de Tecidos, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Ribeiro, R.A. [Laboratório da Inflamação e Câncer, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Bertolini, L.R. [Laboratório de Biologia Molecular e do Desenvolvimento, Universidade de Fortaleza, Fortaleza, CE (Brazil); Lima, A.A.M. [Laboratório de Doenças Infecciosas, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Brito, G.A.C. [Laboratório da Inflamação e Câncer, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil); Oriá, R.B. [Laboratório da Biologia da Cicatrização, Ontogenia e Nutrição de Tecidos, INCT - Instituto de Biomedicina do Semiárido Brasileiro, Faculdade de Medicina, Universidade Federal do Ceará, Fortaleza, CE (Brazil)

    2015-04-28

    Apolipoprotein E (APOE=gene, apoE=protein) is a known factor regulating the inflammatory response that may have regenerative effects during tissue recovery from injury. We investigated whether apoE deficiency reduces the healing effect of alanyl-glutamine (Ala-Gln) treatment, a recognized gut-trophic nutrient, during tissue recovery after 5-FU-induced intestinal mucositis. APOE-knockout (APOE{sup -/-}) and wild-type (APOE{sup +/+}) C57BL6J male and female mice (N=86) were given either Ala-Gln (100 mM) or phosphate buffered saline (PBS) by gavage 3 days before and 5 days after a 5-fluorouracil (5-FU) challenge (450 mg/kg, via intraperitoneal injection). Mouse body weight was monitored daily. The 5-FU cytotoxic effect was evaluated by leukometry. Intestinal villus height, villus/crypt ratio, and villin expression were monitored to assess recovery of the intestinal absorptive surface area. Crypt length, mitotic, apoptotic, and necrotic crypt indexes, and quantitative real-time PCR for insulin-like growth factor-1 (IGF-1) and B-cell lymphoma 2 (Bcl-2) intestinal mRNA transcripts were used to evaluate intestinal epithelial cell turnover. 5-FU challenge caused significant weight loss and leukopenia (P<0.001) in both mouse strains, which was not improved by Ala-Gln. Villus blunting, crypt hyperplasia, and reduced villus/crypt ratio (P<0.05) were found in all 5-FU-challenged mice but not in PBS controls. Ala-Gln improved villus/crypt ratio, crypt length and mitotic index in all challenged mice, compared with PBS controls. Ala-Gln improved villus height only in APOE{sup -/-} mice. Crypt cell apoptosis and necrotic scores were increased in all mice challenged by 5-FU, compared with untreated controls. Those scores were significantly lower in Ala-Gln-treated APOE{sup +/+} mice than in controls. Bcl-2 and IGF-1 mRNA transcripts were reduced only in the APOE{sup -/-}-challenged mice. Altogether our findings suggest APOE-independent Ala-Gln regenerative effects after 5-FU

  11. ACE Inhibitor-Induced Angioedema of the Intestine: Case Report, Incidence, Pathophysiology, Diagnosis and Management

    Directory of Open Access Journals (Sweden)

    Gavin Oudit

    2001-01-01

    Full Text Available A case report of fosinopril-induced angioedema of the intestine with a chronic course accompanied by multiple acute exacerbations is described. Angiotensin-converting enzyme (ACE inhibitor-induced angioedema of the intestine (AIAI occurs in a minority of patients taking an ACE inhibitor. The clinical presentation encompasses acute abdominal symptoms, pronounced bowel edema and ascites with occasional facial and/or oropharyngeal swelling. AIAI is diagnosed based on the temporal relationship between the symptomatic presentation and drug use, absence of alternative diagnoses including other causes of angioedema, and the prompt resolution of symptoms upon discontinuation of the ACE inhibitor. Prompt radiological investigation (abdominal computerized tomography and/or ultrasound is critical in making an early diagnosis and in preventing unnecessary surgical intervention. There is a female predominance of AIAI, which may reflect the interaction of estradiol with the various pathways involved in the pathophysiology of AIAI. Management of AIAI consists mainly of conservative measures and discontinuation of the ACE inhibitor. Angiotensin II receptor antagonists should not be considered as appropriate alternatives. Awareness and knowledge of AIAI are important because of the increasing use of ACE inhibitors, current delays in making the diagnosis, obvious management strategies once the diagnosis is made and the dysutility of alternative diagnoses, which may lead to considerable morbidity. AIAI must be considered in patients taking ACE inhibitors who develop gastrointestinal complaints irrespective of the duration of the therapy.

  12. Fasting-induced intestinal damage is mediated by oxidative and inflammatory responses.

    Science.gov (United States)

    Abdeen, S; Mathew, T C; Khan, I; Dashti, H; Asfar, S

    2009-05-01

    Green tea has been shown to repair fasting-induced mucosal damage in rat intestine. The aim of this study was to elucidate the underlying mechanism. Five groups of rats were used. Group 1 had free access to chow diet and water, and those in group 2 were fasted for 3 days. Animals in group 3 were fasted for 3 days, then were allowed drinking water for a further 7 days. Groups 4 and 5 were fasted for 3 days, then given drinking water containing green tea or vitamin E respectively for 7 days. Blood was collected for estimation of total plasma antioxidants, and jejunal samples were used for immunohistochemical analysis of superoxide dismutase (SOD), catalase and glutathione peroxidase (GPx), and for estimation of myeloperoxidase (MPO) activity. Use of green tea was associated with a significant increase in total plasma antioxidants (P fasting-induced damage to the intestinal mucosa by its antioxidant and anti-inflammatory effect. 2009 British Journal of Surgery Society Ltd. Published by John Wiley & Sons, Ltd.

  13. Gastroprotective effect of esculin on ethanol-induced gastric lesion in mice.

    Science.gov (United States)

    Li, Weifeng; Wang, Yu; Wang, Xiumei; Zhang, Hailin; He, Zehong; Zhi, Wenbing; Liu, Fang; Niu, Xiaofeng

    2017-04-01

    The gastroprotective effect of esculin was investigated in a mouse model of ethanol-induced gastric lesion. Administration of esculin at doses of 5, 10, and 20 mg/kg body weight prior to ethanol ingestion led to significant gastroprotection compared with untreated mice. Gastric mucosal lesions were evaluated by macroscopic and histopathological alterations, lesion index, and myeloperoxidase (MPO) activity. Pretreatment with esculin significantly reduced macroscopic and histopathological damage, gastric lesion index, and MPO activity in a dose-dependent manner. Moreover, esculin significantly reduced nitric oxide (NO) production, inducible NO synthase (iNOS) levels, and nuclear factor-kappa B (NF-κB) p65 protein expression in gastric tissues after ethanol challenge. Analysis of inflammatory cytokines indicated that esculin pretreatment markedly suppressed the increased expression of tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6) in ethanol-treated mice. The results demonstrate a protective effect of esculin against gastric injury and suggest that the underlying mechanism might be associated with inhibition of NF-κB activation, which subsequently reduces expression of iNOS, TNF-α, and IL-6. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  14. Oxidized low density lipoprotein induced caspase-1 mediated pyroptotic cell death in macrophages: implication in lesion instability?

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    Jing Lin

    Full Text Available BACKGROUND: Macrophage death in advanced lesion has been confirmed to play an important role in plaque instability. However, the mechanism underlying lesion macrophage death still remains largely unknown. METHODS AND RESULTS: Immunohistochemistry showed that caspase-1 activated in advanced lesion and co-located with macrophages and TUNEL positive reaction. In in-vitro experiments showed that ox-LDL induced caspase-1 activation and this activation was required for ox-LDL induced macrophages lysis, IL-1β and IL-18 production as well as DNA fragmentation. Mechanism experiments showed that CD36 and NLRP3/caspase-1/pathway involved in ox-LDL induced macrophage pyroptosis. CONCLUSION: Our study here identified a novel cell death, pyroptosis in ox-LDL induced human macrophage, which may be implicated in lesion macrophages death and play an important role in lesion instability.

  15. Giardia duodenalis Surface Cysteine Proteases Induce Cleavage of the Intestinal Epithelial Cytoskeletal Protein Villin via Myosin Light Chain Kinase.

    Directory of Open Access Journals (Sweden)

    Amol Bhargava

    Full Text Available Giardia duodenalis infections are among the most common causes of waterborne diarrhoeal disease worldwide. At the height of infection, G. duodenalis trophozoites induce multiple pathophysiological processes within intestinal epithelial cells that contribute to the development of diarrhoeal disease. To date, our understanding of pathophysiological processes in giardiasis remains incompletely understood. The present study reveals a previously unappreciated role for G. duodenalis cathepsin cysteine proteases in intestinal epithelial pathophysiological processes that occur during giardiasis. Experiments first established that Giardia trophozoites indeed produce cathepsin B and L in strain-dependent fashion. Co-incubation of G. duodenalis with human enterocytes enhanced cathepsin production by Assemblage A (NF and S2 isolates trophozoites, but not when epithelial cells were exposed to Assemblage B (GSM isolate trophozoites. Direct contact between G. duodenalis parasites and human intestinal epithelial monolayers resulted in the degradation and redistribution of the intestinal epithelial cytoskeletal protein villin; these effects were abolished when parasite cathepsin cysteine proteases were inhibited. Interestingly, inhibition of parasite proteases did not prevent degradation of the intestinal tight junction-associated protein zonula occludens 1 (ZO-1, suggesting that G. duodenalis induces multiple pathophysiological processes within intestinal epithelial cells. Finally, this study demonstrates that G. duodenalis-mediated disruption of villin is, at least, in part dependent on activation of myosin light chain kinase (MLCK. Taken together, this study indicates a novel role for parasite cathepsin cysteine proteases in the pathophysiology of G. duodenalis infections.

  16. Sex-dependent Differences in Intestinal Tumorigenesis Induced in Apc1638N/+ Mice by Exposure to {gamma} Rays

    Energy Technology Data Exchange (ETDEWEB)

    Trani, Daniela [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Maastricht Radiation Oncology (MaastRO) Lab, GROW-School for Oncology and Developmental Biology, University of Maastricht (Netherlands); Moon, Bo-Hyun [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Kallakury, Bhaskar; Hartmann, Dan P. [Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Datta, Kamal [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Fornace, Albert J., E-mail: af294@georgetown.edu [Department of Biochemistry and Molecular and Cellular Biology, Georgetown University, Washington, District of Columbia (United States); Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington, District of Columbia (United States); Center of Excellence in Genomic Medicine Research (CEGMR), King Abdulaziz University, Jeddah (Saudi Arabia)

    2013-01-01

    Purpose: The purpose of the present study was to assess the effect of 1 and 5 Gy radiation doses and to investigate the interplay of gender and radiation with regard to intestinal tumorigenesis in an adenomatous polyposis coli (APC) mutant mouse model. Methods and Materials: Apc1638N/+ female and male mice were exposed whole body to either 1 Gy or 5 Gy of {gamma} rays and euthanized when most of the treated mice became moribund. Small and large intestines were processed to determine tumor burden, distribution, and grade. Expression of proliferation marker Ki-67 and estrogen receptor (ER)-{alpha} were also assessed by immunohistochemistry. Results: We observed that, with both 1 Gy and 5 Gy of {gamma} rays, females displayed reduced susceptibility to radiation-induced intestinal tumorigenesis compared with males. As for radiation effect on small intestinal tumor progression, although no substantial differences were found in the relative frequency and degree of dysplasia of adenomas in irradiated animals compared with controls, invasive carcinomas were found in 1-Gy- and 5-Gy-irradiated animals. Radiation exposure was also shown to induce an increase in protein levels of proliferation marker Ki-67 and sex-hormone receptor ER-{alpha} in both non tumor mucosa and intestinal tumors from irradiated male mice. Conclusions: We observed important sex-dependent differences in susceptibility to radiation-induced intestinal tumorigenesis in Apc1638N/+ mutants. Furthermore, our data provide evidence that exposure to radiation doses as low as 1 Gy can induce a significant increase in intestinal tumor multiplicity as well as enhance tumor progression in vivo.

  17. (--Epicatechin protects the intestinal barrier from high fat diet-induced permeabilization: Implications for steatosis and insulin resistance

    Directory of Open Access Journals (Sweden)

    Eleonora Cremonini

    2018-04-01

    Full Text Available Increased permeability of the intestinal barrier is proposed as an underlying factor for obesity-associated pathologies. Consumption of high fat diets (HFD is associated with increased intestinal permeabilization and increased paracellular transport of endotoxins which can promote steatosis and insulin resistance. This study investigated whether dietary (--epicatechin (EC supplementation can protect the intestinal barrier against HFD-induced permeabilization and endotoxemia, and mitigate liver damage and insulin resistance. Mechanisms leading to loss of integrity and function of the tight junction (TJ were characterized. Consumption of a HFD for 15 weeks caused obesity, steatosis, and insulin resistance in male C57BL/6J mice. This was associated with increased intestinal permeability, decreased expression of ileal TJ proteins, and endotoxemia. Supplementation with EC (2–20 mg/kg body weight mitigated all these adverse effects. EC acted modulating cell signals and the gut hormone GLP-2, which are central to the regulation of intestinal permeability. Thus, EC prevented HFD-induced ileum NOX1/NOX4 upregulation, protein oxidation, and the activation of the redox-sensitive NF-κB and ERK1/2 pathways. Supporting NADPH oxidase as a target of EC actions, in Caco-2 cells EC and apocynin inhibited tumor necrosis alpha (TNFα-induced NOX1/NOX4 overexpression, protein oxidation and monolayer permeabilization. Together, our findings demonstrate protective effects of EC against HFD-induced increased intestinal permeability and endotoxemia. This can in part underlie EC capacity to prevent steatosis and insulin resistance occurring as a consequence of HFD consumption. Keywords: Intestinal permeability, (--Epicatechin, Steatosis, Insulin resistance, Endotoxemia, NADPH oxidase

  18. Consequences of PAI-1 specific deletion in endothelium on radiation-induced intestinal damage

    International Nuclear Information System (INIS)

    Rannou, Emilie

    2015-01-01

    Radiation-induced injury to healthy tissues is a real public health problem, since they are one of the most limiting factors that restrict efficiency of radiation therapy. This problematic is also part of the French Cancer Plan 2014-2017, and involves clinical research. Concepts surrounding the development of radiation-induced damage have gradually evolved into a contemporary and integrated view of the pathogenesis, involving all compartments of target tissue. Among them, endothelium seems to be central in the sequence of interrelated events that lead to the development of radiation-induced damage, although there are rare concrete elements that support this concept. By using new transgenic mouse models, this PhD project provides a direct demonstration of an endothelium-dependent continuum in evolution of radiation-induced intestinal damage. Indeed, changes in the endothelial phenotype through targeted deletion of the gene SERPINE1, chosen because of its key role in the development of radiation enteritis, influences various parameters of the development of the disease. Thus, lack of PAI-1 secretion by endothelial cells significantly improves survival of the animals, and limits severity of early and late tissue damage after a localized small bowel irradiation. Furthermore, these mice partially KO for PAI-1 showed a decrease in the number of apoptotic intestinal stem cells in the hours following irradiation, a decrease in the macrophages infiltrate density one week after irradiation, and a change in the polarization of macrophages throughout the pathophysiological process. In an effort to protect healthy tissues from radiation therapy side effects, without hindering the cancer treatment, PAI-1 seems to be an obvious therapeutic target. Conceptually, this work represents the direct demonstration of the link between endothelium phenotype and radiation enteritis pathogenesis. (author)

  19. Honey potentiates the gastric protection effects of sucralfate against ammonia-induced gastric lesions in rats.

    Science.gov (United States)

    Ali, Abu Taib Mohammad Mobarok; Al Swayeh, Othman Abdullah

    2003-09-01

    Natural honey is widely used all over the world as a complementary and alternative medicine in various disorders including gastrointestinal lesions. To evaluate the effects of combination of low dosage of honey (0.312 g/kg) and sucralfate (0.125 or 0.250 g /kg) on gastric protection and to determine any potentiating interactions between them against ammonia-induced gastric lesions in rats. Twenty-four hours fasted rats were given I ml of ammonium hydroxide 1 % intragastrically and they were killed one hour later under deep ether anesthesia. The gastric lesion index was calculated according to the method of Takaishi et al 1998. Non protein sulthydryls level was determined spectrophotometrically as described by Sedlak and Lindsay 1968. Administration of ammonium hydroxide produced red and black linear lesions and significant depletion of gastric nonprotein sulthydryls level. Oral administration of honey (0.312g/kg) or sucralfate (0.125 and 0.250 g/kg) 30 min before ammonium hydroxide reduced the severity of gastric mucosal lesions by 1 I or 18 and 42 % respectively, and has shown the changes in nonprotein sulfhydryls level induced by ammonium hydroxide. Furthermore, pretreatment with a combination of a low dose of honey (0.312 g /kg) and sucralfate (0.125 g or 0.250 g/kg) afforded significantly greater protection (58 and 77 %) than that obtained with either of them administered alone. The present results suggest potentiation of gastric protection effect of sucralfate by honey and this may have a clinical value in the treatment of peptic ulcer diseases in Helicobacter pylori positive patients.

  20. [Intelligence and creativity changes induced by pathological growth of space-occupying cerebral lesion].

    Science.gov (United States)

    Perfil'ev, A M; Razumnikova, O M; Stupak, V V

    2013-01-01

    Creativity and intelligence changes depending on tumor localization in frontal or parietal cortex before surgical procedure in 24 patients in comparison with control group are studied. Brain damage-induced intelligence impairment and a decrease of fluency, flexibility of figural divergent thinking, and originality of verbal one without specificity of tumor localization were found. Intelligence decrease was more presented while performing of figural tasks and least of all in verbal ones. The left prefrontal brain damage induced a decrease of all components of intelligence and a trend to a decrease of verbal creativity and figural fluency. The right parietal brain lesion was more associated with a decline of divergent thinking originality.

  1. Mucoadhesive formulation of Bidens pilosa L. (Asteraceae reduces intestinal injury from 5-fluorouracil-induced mucositis in mice

    Directory of Open Access Journals (Sweden)

    Paulo Henrique Marcelino de Ávila

    2015-01-01

    Full Text Available Gastrointestinal mucositis induced during cancer treatment is considered a serious dose-limiting side effect of chemotherapy and/or radiotherapy. Frequently, interruption of the cancer treatment due to this pathology leads to a reduction in cure rates, increase of treatment costs and decrease life quality of the patient. Natural products such as Bidens pilosa L. (Asteraceae, represent a potential alternative for the treatment of mucositis given its anti-inflammatory properties. In this study, B. pilosa glycolic extract was formulated (BPF with poloxamer, a mucoadhesive copolymer, was used for treatment of 5-fluorouracil (5-FU-induced mucositis in mice. As expected, animals only treated with 5-FU (200 mg/kg presented marked weight loss, reduction of intestinal villi, crypts and muscular layer, which was associated with severe disruption of crypts, edema, inflammatory infiltrate and vacuolization in the intestinal tissue, as compared to the control group and healthy animals only treated with BPF. On the other hand, the treatment of intestinal mucositis-bearing mice with BPF (75, 100 or 125 mg/kg managed to mitigate clinical and pathologic changes, noticeably at 100 mg/kg. This dose led to the restoration of intestinal proliferative activity through increasing Ki-67 levels; modulated the expression of Bax, Bcl2 and p53 apoptotic markers protecting intestinal cells from cell death. Moreover, this treatment regulated lipid peroxidation and inflammatory infiltration. No acute toxic effects were observed with this formulation. This work demonstrated that BPF was safe and effective against 5-FU-induced intestinal mucositis in mice. Additional studies are already in progress to further characterize the mechanisms involved in the protective effects of this technological formulation toward the development of a new medicine for the prevention and treatment of intestinal injury in patients undergoing chemotherapy/radiotherapy.

  2. Angiotensin II induces apoptosis in intestinal epithelial cells through the AT2 receptor, GATA-6 and the Bax pathway

    International Nuclear Information System (INIS)

    Sun, Lihua; Wang, Wensheng; Xiao, Weidong; Liang, Hongyin; Yang, Yang; Yang, Hua

    2012-01-01

    Highlights: ► Ang II-induced apoptosis in intestinal epithelial cell through AT2 receptor. ► The apoptosis process involves in the Bax/Bcl-2 intrinsic pathway. ► GATA-6 short hairpin RNA reduced Bax expression, but not Bcl-2. ► GATA-6 may play a critical role in apoptosis in response to the Ang II challenge. -- Abstract: Angiotensin II (Ang II) has been shown to play an important role in cell apoptosis. However, the mechanisms of Ang-II-induced apoptosis in intestinal epithelial cells are not fully understood. GATA-6 is a zinc finger transcription factor expressed in the colorectal epithelium, which directs cell proliferation, differentiation and apoptosis. In the present study we investigated the underlying mechanism of which GATA-6 affects Ang-II induced apoptosis in intestinal epithelial cells. The in vitro intestinal epithelial cell apoptosis model was established by co-culturing Caco-2 cells with Ang II. Pretreatment with Angiotensin type 2 (AT2) receptor antagonist, PD123319, significantly reduced the expression of Bax and prevented the Caco-2 cells apoptosis induced by Ang II. In addition, Ang II up-regulated the expression of GATA-6. Interestingly, GATA-6 short hairpin RNA prevented Ang II-induced intestinal epithelial cells apoptosis and reduced the expression of Bax, but not Bcl-2. Taken together, the present study suggests that Angiotensin II promotes apoptosis in intestinal epithelial cells through GATA-6 and the Bax pathway in an AT2 receptor-dependent manner.

  3. Characterization and pharmacological modulation of intestinal inflammation induced by ionizing radiation

    International Nuclear Information System (INIS)

    Gremy, O.

    2006-12-01

    The use of radiation therapy to treat abdominal and pelvic malignancies inevitably involves exposure of healthy intestinal tissues which are very radiosensitive. As a result, most patients experience symptoms such as abdominal pain, nausea and diarrhea. Such symptoms are associated with acute damage to intestine mucosa including radio-induced inflammatory processes. With a rat model of colorectal fractionated radiation, we have shown a gradual development of a colonic inflammation during radiation planning, without evident tissue injury. This radio-induced inflammation is characterized not only by the sur expressions of pro-inflammatory cytokines and chemokines, a NF-kB activation, but also by a repression of anti-inflammatory cytokines and the nuclear receptors PPARa and RXRa, both involved in inflammation control. This early inflammation is associated with a discreet neutrophil recruitment and a macrophage accumulation. Macrophages are still abnormally numerous in tissue 27 weeks after the last day of irradiation. Inflammatory process is the most often related to a specific immune profile, either a type Th1 leading to a cellular immune response, or a type Th2 for humoral immunity. According to our studies, a unique abdominal radiation in the rat induces an ileum inflammation and an immune imbalance resulting in a Th2-type profile. Inhibiting this profile is important as its persistence promotes chronic inflammation, predisposition to bacterial infections and fibrosis which is the main delayed side-effect of radiotherapy. The treatment of rats with an immuno-modulator compound, the caffeic acid phenethyl ester (C.A.P.E.), have the potential to both reduce ileal mucosal inflammation and inhibit the radio-induced Th2 status. In order to search new therapeutic molecular target, we has been interested in the PPARg nuclear receptor involved in the maintenance of colon mucosal integrity. In our abdominal irradiation model, we have demonstrated that the prophylactic

  4. DNA radio-induced tandem lesions: formation, introduction in oligonucleotides and repair

    International Nuclear Information System (INIS)

    Bourdat, Anne-Gaelle

    2000-01-01

    Cell killing induced by excited photosensitizers, ionizing radiation or radiomimetic drugs can not be only explained by the formation of single DNA lesions. Thus, multiply damaged sites, are likely to have harmful biological consequences. One example of tandem base damage induced by ".OH radical in X-irradiated aqueous solution of DNA oligomers is N-(2-deoxy-β-D-erythro-pentofuranosyl)-formyl-amine (dβF)/8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodGuo). In order to investigate the biological significance of such a tandem lesion, both 8-oxodGuo and dβF were introduced in synthetic oligonucleotides at vicinal positions using the solid phase phosphoramidite method with the 'Pac phosphoramidite' chemistry. The purity of the synthetic DNA fragments and the integrity of modified nucleosides was confirmed using different complementary techniques: HPLC, PAGE, ESI MS, MALDI-TOF MS and capillary electrophoresis. Using the above synthetic substrates, investigations were carried out in order to determine the substrate specificity and the excision mechanism of three glycosylases involved in the base excision repair pathway: endonuclease III, Fpg and yOggl. Both tandem lesions were substrates for the BER enzymes. However, the tandem lesion are not completely excised by the repair enzymes. The rates of excision as inferred from the determination of the ratios of Vm/Km Michaelis kinetics constants were not found to be significantly affected by the presence of the tandem lesions. MALDI-TOF mass spectrometry was used in order to gain insights into mechanistic aspects of oligonucleotide cleavage by the BER enzymes. During in vitro DNA synthesis by Taq DNA polymerase, Klenow fragment exo- and DNA polymerase β, tandem base damage were found to block the progression of the enzymes. Finally, the level of tandem base damage in the DNA exposed to γ-ray using the liquid chromatography coupled to electro-spray ionization tandem mass spectrometry was determined. Both dβF-8-oxodGuo and 8

  5. Methyl and isopropyl N-methylanthranilates attenuate diclofenac- and ethanol-induced gastric lesions in rats.

    Science.gov (United States)

    Radulović, Niko S; Jovanović, Ivan; Ilić, Ivan R; Randjelović, Pavle J; Stojanović, Nikola M; Miltojević, Ana B

    2013-11-19

    Two natural alkaloids, methyl (M) and isopropyl (I) N-methylanthranilates, with recently demonstrated significant pharmacological activities, were assayed for their possible overall effect on intact gastric mucosa and their protective properties towards the onset of gastric lesions induced by diclofenac (a non-steroidal anti-inflammatory drug, NSAID) or ethanol. The influence of I and M on gastric mucosa integrity was assessed by oral administration in doses of 200mg/kg. The gastroprotective action of I and M in doses of 50, 100 and 200mg/kg was analyzed in the diclofenac and ethanol-induced gastric lesion models in rats. After the treatment, the stomachs of the animals were analyzed (captured by a digital camera). Ulcer scoring, morphometric and histopathological analyses of the stomachs were done. The oral application of these compounds on their own, even in quite high doses (200mg/kg) did not induce gastric lesions. Both alkaloids exerted a very strong antiulcer activity, even in low doses (50mg/kg), by decreasing the number of lesions caused by the application of either diclofenac or ethanol, eliminating them completely or reducing them to a form of mucosal hyperemia. Their possible mechanism of action was discussed and due to their many positive properties including anxiolytic, antidepressant, antinociceptive, anti-inflammatory and gastroprotective activities, as well as a cheap and simple synthetic route for their preparation, methyl and isopropyl N-methylanthranilates, both alike, might represent a cost effective alternative sought for in the treatment of peptic ulcers and/or new safer NSAIDs for pain management. © 2013.

  6. Nivalenol induces oxidative stress and increases deoxynivalenol pro-oxidant effect in intestinal epithelial cells

    Energy Technology Data Exchange (ETDEWEB)

    Del Regno, Marisanta; Adesso, Simona; Popolo, Ada [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy); Quaroni, Andrea [Department of Biomedical Sciences, Cornell University, Veterinary Research Tower, Cornell University, Ithaca, NY 14853–6401 (United States); Autore, Giuseppina [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy); Severino, Lorella [Department of Pathology and Animal Health, Division of Toxicology, School of Veterinary Medicine, University of Naples “Federico II”, Via Delpino 1, 80137 Naples (Italy); Marzocco, Stefania, E-mail: smarzocco@unisa.it [Department of Pharmacy, School of Pharmacy, University of Salerno, Via Giovanni Paolo II, 132–84084 Fisciano, Salerno (Italy)

    2015-06-01

    Mycotoxins are secondary fungal metabolites often found as contaminants in almost all agricultural commodities worldwide, and the consumption of food or feed contaminated by mycotoxins represents a major risk for human and animal health. Reactive oxygen species are normal products of cellular metabolism. However, disproportionate generation of reactive oxygen species poses a serious problem to bodily homeostasis and causes oxidative tissue damage. In this study we analyzed the effect of two trichothecenes mycotoxins: nivalenol and deoxynivalenol, alone and in combination, on oxidative stress in the non-tumorigenic intestinal epithelial cell line IEC-6. Our results indicate the pro-oxidant nivalenol effect in IEC-6, the stronger pro-oxidant effect of nivalenol when compared to deoxynivalenol and, interestingly, that nivalenol increases deoxynivalenol pro-oxidative effects. Mechanistic studies indicate that the observed effects were mediated by NADPH oxidase, calcium homeostasis alteration, NF-kB and Nrf2 pathways activation and by iNOS and nitrotyrosine formation. The toxicological interaction by nivalenol and deoxynivalenol reported in this study in IEC-6, points out the importance of the toxic effect of these mycotoxins, mostly in combination, further highlighting the risk assessment process of these toxins that are of growing concern. - Highlights: • Nivalenol induces oxidative stress in intestinal epithelial cells (IECs). • Nivalenol increases deoxynivalenol pro-oxidant effects in IECs. • Nivalenol and deoxynivalenol trigger antioxidant response IECs. • These results indicate the importance of mycotoxins co-contamination.

  7. The protective effect of infliximab on cisplatin-induced intestinal tissue toxicity.

    Science.gov (United States)

    Aydin, I; Kalkan, Y; Ozer, E; Yucel, A F; Pergel, A; Cure, E; Cure, M C; Sahin, D A

    2014-01-01

    Cisplatin (CP) is a popular chemotherapeutic agent. However, high doses of CP may lead to severe side effects to the gastrointestinal system. The aim of this study was to investigate the protective effects of infliximab on small intestine injury induced by high doses of CP. The A total of 30 rats were equally divided into three groups, including sham (C), cisplatin (CP), and cisplatin + infliximab (CPI). The CP group was treated with 7 mg/kg intraperitoneal cisplatin, and a laparotomy was performed 5 days later. The CPI group received 7 mg/kg infliximab intraperitoneally, were administered 7 mg/kg cisplatin 4 days later, and a laparotomy was performed 5 days after receiving cisplatin. Histopathological and immunohistochemical analysis of small intestine tissue sections were performed, and superoxide dismutase, malondialdehyde, and TNF-α levels were measured. Histopathological evaluation revealed that the CP group had damage in the epithelium and connective tissue, but this damage was significantly improved in the CPI group (p < 0.05). In addition, these histopathological findings were confirmed by biochemical analyses. These results suggest that infliximab is protective against the adverse effects of CP.

  8. Assessment of Mycoplasma hyopneumoniae-induced Pneumonia using Different Lung Lesion Scoring Systems: a Comparative Review.

    Science.gov (United States)

    Garcia-Morante, B; Segalés, J; Fraile, L; Pérez de Rozas, A; Maiti, H; Coll, T; Sibila, M

    2016-01-01

    Mycoplasma hyopneumoniae is the primary aetiological agent of swine enzootic pneumonia (EP) and one of the major contributors to the porcine respiratory disease complex (PRDC). Gross lung lesions in pigs affected by EP consist of cranioventral pulmonary consolidation (CVPC), usually distributed bilaterally in the apical, intermediate, accessory and cranial parts of the diaphragmatic lobes. Several lung scoring methods are currently in place for the evaluation of CVPC. The aims of this study were (1) to review the lung lesion scoring systems used to assess pneumonia associated with M. hyopneumoniae infection, and (2) to evaluate eight of these scoring systems by applying them to the lungs of 76 pigs with experimentally-induced M. hyopneumoniae pneumonia. A significant correlation between all lung lesion scoring systems was observed and the coefficients of determination in a regression analysis were very high between each pair-wise comparison, except for a unique scoring system based on image analysis. A formula of equivalence between lung scoring methods was developed in order to compare the results obtained with these methods. The present review provides a basis for comparison (even retrospectively) of lesions evaluated using different lung scoring systems. Copyright © 2015. Published by Elsevier Ltd.

  9. [Peripheral facial nerve lesion induced long-term dendritic retraction in pyramidal cortico-facial neurons].

    Science.gov (United States)

    Urrego, Diana; Múnera, Alejandro; Troncoso, Julieta

    2011-01-01

    Little evidence is available concerning the morphological modifications of motor cortex neurons associated with peripheral nerve injuries, and the consequences of those injuries on post lesion functional recovery. Dendritic branching of cortico-facial neurons was characterized with respect to the effects of irreversible facial nerve injury. Twenty-four adult male rats were distributed into four groups: sham (no lesion surgery), and dendritic assessment at 1, 3 and 5 weeks post surgery. Eighteen lesion animals underwent surgical transection of the mandibular and buccal branches of the facial nerve. Dendritic branching was examined by contralateral primary motor cortex slices stained with the Golgi-Cox technique. Layer V pyramidal (cortico-facial) neurons from sham and injured animals were reconstructed and their dendritic branching was compared using Sholl analysis. Animals with facial nerve lesions displayed persistent vibrissal paralysis throughout the five week observation period. Compared with control animal neurons, cortico-facial pyramidal neurons of surgically injured animals displayed shrinkage of their dendritic branches at statistically significant levels. This shrinkage persisted for at least five weeks after facial nerve injury. Irreversible facial motoneuron axonal damage induced persistent dendritic arborization shrinkage in contralateral cortico-facial neurons. This morphological reorganization may be the physiological basis of functional sequelae observed in peripheral facial palsy patients.

  10. Is the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex important for motor recovery in rats with photochemically induced cortical lesions?

    Science.gov (United States)

    Takata, Kotaro; Yamauchi, Hideki; Tatsuno, Hisashi; Hashimoto, Keiji; Abo, Masahiro

    2006-01-01

    To determine whether the ipsilateral cortex surrounding the lesion or the non-injured contralateral cortex is important for motor recovery after brain damage in the photochemically initiated thrombosis (PIT) model. We induced PIT in the sensorimotor cortex in rats and examined the recovery of motor function using the beam-walking test. In 24 rats, the right sensorimotor cortex was lesioned after 2 days of training for the beam-walking test (group 1). After 10 days, PIT was induced in the left sensorimotor cortex. Eight additional rats (group 2) received 2 days training in beam walking, then underwent the beam-walking test to evaluate function. After 10 days of testing, the left sensorimotor cortex was lesioned and recovery was monitored by the beam-walking test for 8 days. In group 1 animals, left hindlimb function caused by a right sensorimotor cortex lesion recovered within 10 days after the operation. Right hindlimb function caused by the left-side lesion recovered within 6 days. In group 2, right hindlimb function caused by induction of the left-side lesion after a total of 12 days of beam-walking training and testing recovered within 6 days as with the double PIT model. The training effect may be relevant to reorganization and neuromodulation. Motor recovery patterns did not indicate whether motor recovery was dependent on the ipsilateral cortex surrounding the lesion or the cortex of the contralateral side. The results emphasize the need for selection of appropriate programs tailored to the area of cortical damage in order to enhance motor functional recovery in this model. Copyright 2006 S. Karger AG, Basel.

  11. Gastroprotective effect of Cymbopogon citratus infusion on acute ethanol-induced gastric lesions in rats.

    Science.gov (United States)

    Sagradas, Joana; Costa, Gustavo; Figueirinha, Artur; Castel-Branco, Maria Margarida; Silvério Cabrita, António Manuel; Figueiredo, Isabel Vitória; Batista, Maria Teresa

    2015-09-15

    Treatment of gastric ulcers with medicinal plants is quite common in traditional medicine worldwide. Cymbopogon citratus (DC) Stapf. leaves infusion has been used in folk medicine of many tropical and subtropical regions to treat gastric disturbances. The aim of this study was to assess the potential gastroprotective activity of an essential oil-free infusion from C. citratus leaves in acute gastric lesions induced by ethanol in rat. The study was performed on adult male Wistar rats (234.0±22.7g) fasted for 24h but with free access to water. The extract was given orally before (prevention) or after (treatment) intragastric administration of absolute ethanol. Effects of dose (28 or 56mg/kg of body weight) and time of contact of the extract with gastric mucosa (1 or 2h) were also assessed. Animals were sacrificed, being the stomachs removed and the lesions were assessed by macroscopic observation and histopathology. C. citratus extract, given orally before or after ethanol, significantly (P<0.01) reduced gastric mucosal injury compared with control group (vehicle+ethanol). The effect does not appear to be dose-dependent. Results also suggested that the extract is more effective when the time of contact with gastric mucosa increases. The results of this assay confirm the gastroprotective activity of C. citratus extract on experimental gastric lesions induced by ethanol, contributing for the pharmacological validation of its traditional use. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  12. Ascorbic acid deficiency aggravates stress-induced gastric mucosal lesions in genetically scorbutic ODS rats.

    Science.gov (United States)

    Ohta, Y; Chiba, S; Imai, Y; Kamiya, Y; Arisawa, T; Kitagawa, A

    2006-12-01

    We examined whether ascorbic acid (AA) deficiency aggravates water immersion restraint stress (WIRS)-induced gastric mucosal lesions in genetically scorbutic ODS rats. ODS rats received scorbutic diet with either distilled water containing AA (1 g/l) or distilled water for 2 weeks. AA-deficient rats had 12% of gastric mucosal AA content in AA-sufficient rats. AA-deficient rats showed more severe gastric mucosal lesions than AA-sufficient rats at 1, 3 or 6 h after the onset of WIRS, although AA-deficient rats had a slight decrease in gastric mucosal AA content, while AA-sufficient rats had a large decrease in that content. AA-deficient rats had more decreased gastric mucosal nonprotein SH and vitamin E contents and increased gastric mucosal lipid peroxide content than AA-sufficient rats at 1, 3 or 6 h of WIRS. These results indicate that AA deficiency aggravates WIRS-induced gastric mucosal lesions in ODS rats by enhancing oxidative damage in the gastric mucosa.

  13. Distribution of ultraviolet-induced lesions in Simian Virus 40 DNA

    International Nuclear Information System (INIS)

    Bourre, F.; Renault, G.; Sarasin, A.; Seawell, P.C.

    1985-01-01

    In order to analyze the molecular mechanisms of mutagenesis in mammalian cells, we devised an analytical assay using Simian Virus 40 as biological probe. To study the possible correlations between the distribution of the lesions on the treated DNA and the distribution of mutations, we have located and quantified the lesions induced by ultraviolet light (254 nm) on a SV40 DNA fragment. At a fluence of 2,000J/m 2 , our results show that the formation frequency of thymine-thymine dimers (TT) is three to four times higher than the formation frequency of the other types of dimers (TC, CT, CC). On the other hand, the formation frequency of a dimer is influenced by the adjacent sequence. In particular, a pyrimidine in the 5' position of a thymine-thymine dimer enhances its formation frequency. At the dose used the formation frequency of the pyrimidine (6-4) pyrimidone photoproducts is twenty times less than the formation frequency of pyrimidine dimers. This paper shows the distribution of the major lesions induced by UV-light on a defined fragment of SV40 genome after UV irradiation. This work is necessary to get an insight in the molecular mechanisms of UV-mutagenesis

  14. UVA photoactivation of DNA containing halogenated thiopyrimidines induces cytotoxic DNA lesions

    Science.gov (United States)

    Brem, Reto; Zhang, Xiaohui; Xu, Yao-Zhong; Karran, Peter

    2015-01-01

    Photochemotherapy, the combination of a photosensitiser and ultraviolet (UV) or visible light, is an effective treatment for skin conditions including cancer. The high mutagenicity and non-selectivity of photochemotherapy regimes warrants the development of alternative approaches. We demonstrate that the thiopyrimidine nucleosides 5-bromo-4-thiodeoxyuridine (SBrdU) and 5-iodo-4-thiodeoxyuridine (SIdU) are incorporated into the DNA of cultured human and mouse cells where they synergistically sensitise killing by low doses of UVA radiation. The DNA halothiopyrimidine/UVA combinations induce DNA interstrand crosslinks, DNA-protein crosslinks, DNA strand breaks, nucleobase damage and lesions that resemble UV-induced pyrimidine(6-4)pyrimidone photoproducts. These are potentially lethal DNA lesions and cells defective in their repair are hypersensitive to killing by SBrdU/UVA and SIdU/UVA. DNA SIdU and SBrdU generate lethal DNA photodamage by partially distinct mechanisms that reflect the different photolabilities of their C–I and C–Br bonds. Although singlet oxygen is involved in photolesion formation, DNA SBrdU and SIdU photoactivation does not detectably increase DNA 8-oxoguanine levels. The absence of significant collateral damage to normal guanine suggests that UVA activation of DNA SIdU or SBrdU might offer a strategy to target hyperproliferative skin conditions that avoids the extensive formation of a known mutagenic DNA lesion. PMID:25747491

  15. The Effect of Acupuncture and Electro-acupuncture at ST41 on Intestinal Hypomotility Induced with Loperamide in Rats

    Directory of Open Access Journals (Sweden)

    Lee Sang-mi

    2009-12-01

    Full Text Available Objectives : The purpose of this study was to compare the effect of acpuncture and electro-acupuncture of low(EA(L and high(EA(H frequency at Haegye(ST41 on intestinal hypomotility induced with loperamide in rats. Methods : We made suppressed state of intestinal motility with loperamide in rats and carried out needle retention acupuncture, low frequency electro-acupuncture and high frequency electro-acupuncture at ST41 in rats devided into pre-treatment group and post-treatment group. We fed charcoal to them after the treatment and measured the travel rate of charcoal in the gastrointestinal track to analyze which treatment is more effective in state of intestinal hypomotility. Results : None of acupuncture, EA(L and EA(H at ST41 had significant influences on intestinal motility of rat in normal state. Needle retention at ST41 did not significantly increase intestinal motility suppressed with loperamide in rats. Pre-treatment of EA(L and EA(H at ST41 significantly increased intestinal motility suppressed with loperamide in rats. Post-treatment of EA(L and EA(H at ST41 did not have significant influences on intestinal motility of rat in normal state. Conclusions : These results suggest that treatment of EA(L and EA(H at ST41 may be effective on gastric disorders such as intestinal hypomotility and its effect had more prevention than cure. Further study is necessary to know more effects of ST41 and electro-acupuncture of low and high frequency.

  16. Saponin-containing subfractions of soybean molasses induce enteritis in the distal intestine of Atlantic salmon

    DEFF Research Database (Denmark)

    Knudsen, D.; Uran, P.; Arnous, Anis

    2007-01-01

    The current work aimed at tracing the causative components for soybean-induced enteritis in Atlantic salmon (Salmo salar L.). Soybean molasses was subjected to phase separation using n-butanol. Three subfractions were obtained as follows: butanol phase, precipitate, and water phase. The biochemical......-phase high-performance liquid chromatography. Finally, sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to evaluate the size distribution of the proteins present in each fraction. Molasses and the different subfractions were thereafter fed to Atlantic salmon in two successive fish trials....... The level of intestinal inflammation was evaluated by light microscopy using a semiquantitative scoring system. Histological assessments revealed that Atlantic salmon fed a combination of butanol phase and precipitate displayed significant enteritis. Atlantic salmon fed the water phase displayed normal...

  17. Glucagon-like peptide-2 induces rapid digestive adaptation following intestinal resection in preterm neonates

    Science.gov (United States)

    Short bowel syndrome (SBS) is a frequent complication after intestinal resection in infants suffering from intestinal disease. We tested whether treatment with the intestinotrophic hormone glucagon-like peptide-2 (GLP-2) increases intestinal volume and function in the period immediately following in...

  18. Thyroid Hormone-Induced Activation of Notch Signaling is Required for Adult Intestinal Stem Cell Development During Xenopus Laevis Metamorphosis.

    Science.gov (United States)

    Hasebe, Takashi; Fujimoto, Kenta; Kajita, Mitsuko; Fu, Liezhen; Shi, Yun-Bo; Ishizuya-Oka, Atsuko

    2017-04-01

    In Xenopus laevis intestine during metamorphosis, the larval epithelial cells are removed by apoptosis, and the adult epithelial stem (AE) cells appear concomitantly. They proliferate and differentiate to form the adult epithelium (Ep). Thyroid hormone (TH) is well established to trigger this remodeling by regulating the expression of various genes including Notch receptor. To study the role of Notch signaling, we have analyzed the expression of its components, including the ligands (DLL and Jag), receptor (Notch), and targets (Hairy), in the metamorphosing intestine by real-time reverse transcription-polymerase chain reaction and in situ hybridization or immunohistochemistry. We show that they are up-regulated during both natural and TH-induced metamorphosis in a tissue-specific manner. Particularly, Hairy1 is specifically expressed in the AE cells. Moreover, up-regulation of Hairy1 and Hairy2b by TH was prevented by treating tadpoles with a γ-secretase inhibitor (GSI), which inhibits Notch signaling. More importantly, TH-induced up-regulation of LGR5, an adult intestinal stem cell marker, was suppressed by GSI treatment. Our results suggest that Notch signaling plays a role in stem cell development by regulating the expression of Hairy genes during intestinal remodeling. Furthermore, we show with organ culture experiments that prolonged exposure of tadpole intestine to TH plus GSI leads to hyperplasia of secretory cells and reduction of absorptive cells. Our findings here thus provide evidence for evolutionarily conserved role of Notch signaling in intestinal cell fate determination but more importantly reveal, for the first time, an important role of Notch pathway in the formation of adult intestinal stem cells during vertebrate development. Stem Cells 2017;35:1028-1039. © 2016 The Authors STEM CELLS published by Wiley Periodicals, Inc. on behalf of AlphaMed Press.

  19. Spinal cord injury-induced immune deficiency syndrome enhances infection susceptibility dependent on lesion level.

    Science.gov (United States)

    Brommer, Benedikt; Engel, Odilo; Kopp, Marcel A; Watzlawick, Ralf; Müller, Susanne; Prüss, Harald; Chen, Yuying; DeVivo, Michael J; Finkenstaedt, Felix W; Dirnagl, Ulrich; Liebscher, Thomas; Meisel, Andreas; Schwab, Jan M

    2016-03-01

    Pneumonia is the leading cause of death after acute spinal cord injury and is associated with poor neurological outcome. In contrast to the current understanding, attributing enhanced infection susceptibility solely to the patient's environment and motor dysfunction, we investigate whether a secondary functional neurogenic immune deficiency (spinal cord injury-induced immune deficiency syndrome, SCI-IDS) may account for the enhanced infection susceptibility. We applied a clinically relevant model of experimental induced pneumonia to investigate whether the systemic SCI-IDS is functional sufficient to cause pneumonia dependent on spinal cord injury lesion level and investigated whether findings are mirrored in a large prospective cohort study after human spinal cord injury. In a mouse model of inducible pneumonia, high thoracic lesions that interrupt sympathetic innervation to major immune organs, but not low thoracic lesions, significantly increased bacterial load in lungs. The ability to clear the bacterial load from the lung remained preserved in sham animals. Propagated immune susceptibility depended on injury of central pre-ganglionic but not peripheral postganglionic sympathetic innervation to the spleen. Thoracic spinal cord injury level was confirmed as an independent increased risk factor of pneumonia in patients after motor complete spinal cord injury (odds ratio = 1.35, P spinal cord injury directly causes increased risk for bacterial infection in mice as well as in patients. Besides obvious motor and sensory paralysis, spinal cord injury also induces a functional SCI-IDS ('immune paralysis'), sufficient to propagate clinically relevant infection in an injury level dependent manner. © The Author (2016). Published by Oxford University Press on behalf of the Guarantors of Brain. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

  20. Oral mucosal lesions, microbial changes, and taste disturbances induced by adjuvant chemotherapy in breast cancer patients

    DEFF Research Database (Denmark)

    Jensen, Siri Beier; Mouridsen, Henning T.; Bergmann, Olav Jonas

    2008-01-01

    OBJECTIVE: The aim of the study was to examine oral mucosal lesions, microbial changes, and taste disturbances induced by adjuvant chemotherapy (CT) in breast cancer patients during and 1 year after treatment. STUDY DESIGN: Forty-five consecutive breast cancer patients, eligible for adjuvant CT...... with cyclophosphamide, epirubicin or methotrexate, and 5-fluorouracil were followed before, during, 6 months and 1 year after CT and were compared to a control group of 31 breast cancer patients not receiving adjuvant CT. RESULTS: During CT, oral mucosal lesions developed including erythema (n = 10, 22%) and ulceration...... (n = 7, 16%). Five patients (11%) were diagnosed with oral candidosis. Scores of dental bacterial plaque and gingival inflammation increased during CT and the oral microbial composition changed towards a more acidophilic flora. Taste disturbances were experienced by 84% (n = 38) of the patients...

  1. Platelet-activating factor induces TLR4 expression in intestinal epithelial cells: implication for the pathogenesis of necrotizing enterocolitis.

    Directory of Open Access Journals (Sweden)

    Antoine Soliman

    Full Text Available Necrotizing enterocolitis (NEC is a leading cause of morbidity and mortality in neonatal intensive care units, however its pathogenesis is not completely understood. We have previously shown that platelet activating factor (PAF, bacteria and TLR4 are all important factors in the development of NEC. Given that Toll-like receptors (TLRs are expressed at low levels in enterocytes of the mature gastrointestinal tract, but were shown to be aberrantly over-expressed in enterocytes in experimental NEC, we examined the regulation of TLR4 expression and signaling by PAF in intestinal epithelial cells using human and mouse in vitro cell lines, and the ex vivo rat intestinal loop model. In intestinal epithelial cell (IEC lines, PAF stimulation yielded upregulation of both TLR4 mRNA and protein expression and led to increased IL-8 secretion following stimulation with LPS (in an otherwise LPS minimally responsive cell line. PAF stimulation resulted in increased human TLR4 promoter activation in a dose dependent manner. Western blotting and immunohistochemical analysis showed PAF induced STAT3 phosphorylation and nuclear translocation in IEC, and PAF-induced TLR4 expression was inhibited by STAT3 and NFκB Inhibitors. Our findings provide evidence for a mechanism by which PAF augments inflammation in the intestinal epithelium through abnormal TLR4 upregulation, thereby contributing to the intestinal injury of NEC.

  2. Small Intestinal Bypass Induces a Persistent Weight-Loss Effect and Improves Glucose Tolerance in Obese Rats.

    Science.gov (United States)

    Cao, Jiaqing; Ren, Quan; Tan, Cai; Duan, Jinyuan

    2017-07-01

    This study investigated the role of proximal small intestinal bypass (PSIB) and distal small intestinal bypass (DSIB) as well as their long-term effects on weight loss and glucose metabolism in high-sugar and high-fat diet-induced obese rats. Sprague-Dawley rats were divided into four groups: PSIB, bypassing 60% of the proximal small intestine length; DSIB, bypassing 60% of the distal small intestine length; sham-operated (Sham) animals; and control animals. All rats were fed a high-sugar and high-fat diet after surgery. The primary outcome measures were body weight, food intake, fasting blood glucose (FBG) levels, oral glucose tolerance test (OGTT), and the insulin tolerance test (ITT). Global body weight (BW) and food intake in the PSIB and DSIB groups were lower than those in the Sham group at postoperative week 2. BW and food intake in the PSIB group were lower than those in the DSIB group at postoperative week 24. The PSIB and DSIB groups exhibited improvement in glucose tolerance at postoperative weeks 4, 8, and 24. The PSIB and DSIB groups exhibited improvement in FBG at postoperative week 24, and only the DSIB group exhibited improvement in insulin sensitivity. This study provides experimental evidence that PSIB surgery induced a better and more persistent weight loss effect than DSIB surgery and that the two types of intestinal bypass surgeries yielded equivalent and stable long-term improvement in glucose tolerance in an obese rat model.

  3. Administration of Protein kinase D1 induce an immunomodulatory effect on lipopolysaccharide-induced intestinal inflammation in a co-culture model of intestinal epithelial Caco-2 cells and RAW 264.7 macrophage cells

    DEFF Research Database (Denmark)

    Nielsen, Ditte Søvsø Gundelund; Fredborg, Marlene; Andersen, Vibeke

    2017-01-01

    the effects of human PKD1 in relation to intestinal inflammation, using a co-culture model of intestinal epithelial Caco-2 cells and RAW264.7 macrophages. An inflammatory response was induced in the macrophages by lipopolysaccharide (LPS), upregulating the expression of tumour necrosis factor alpha (TNF......-α), interleukin- (IL-) 1β, and IL-6 besides increasing the secretion of TNF-α protein. The effect of administering PKD1 to Caco-2 was evaluated in relation to both amelioration of inflammation and the ability to suppress inflammation initiation. Administration of PKD1 (10–100 ng/ml) following induction...

  4. Evaluation of the chemical model of vestibular lesions induced by arsanilate in rats

    International Nuclear Information System (INIS)

    Vignaux, G.; Chabbert, C.; Gaboyard-Niay, S.; Travo, C.; Machado, M.L.; Denise, P.; Comoz, F.; Hitier, M.; Landemore, G.; Philoxène, B.; Besnard, S.

    2012-01-01

    Several animal models of vestibular deficits that mimic the human pathology phenotype have previously been developed to correlate the degree of vestibular injury to cognate vestibular deficits in a time-dependent manner. Sodium arsanilate is one of the most commonly used substances for chemical vestibular lesioning, but it is not well described in the literature. In the present study, we used histological and functional approaches to conduct a detailed exploration of the model of vestibular lesions induced by transtympanic injection of sodium arsanilate in rats. The arsanilate-induced damage was restricted to the vestibular sensory organs without affecting the external ear, the oropharynx, or Scarpa's ganglion. This finding strongly supports the absence of diffusion of arsanilate into the external ear or Eustachian tubes, or through the eighth cranial nerve sheath leading to the brainstem. One of the striking observations of the present study is the complete restructuring of the sensory epithelia into a non sensory epithelial monolayer observed at 3 months after arsanilate application. This atrophy resembles the monolayer epithelia observed postmortem in the vestibular epithelia of patients with a history of lesioned vestibular deficits such as labyrinthectomy, antibiotic treatment, vestibular neuritis, or Ménière's disease. In cases of Ménière's disease, aminoglycosides, and platinum-based chemotherapy, vestibular hair cells are destroyed, regardless of the physiopathological process, as reproduced with the arsanilate model of vestibular lesion. These observations, together with those presented in this study of arsanilate vestibular toxicity, suggest that this atrophy process relies on a common mechanism of degeneration of the sensory epithelia.

  5. Evaluation of the chemical model of vestibular lesions induced by arsanilate in rats

    Energy Technology Data Exchange (ETDEWEB)

    Vignaux, G. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); Chabbert, C.; Gaboyard-Niay, S.; Travo, C. [INSERM U1051, Institut des Neurosciences de Montpellier, Montpellier, F-34090,France (France); Machado, M.L. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); Denise, P. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); CHRU Caen, Explorations Fonctionnelles, Caen, F-14000 (France); Comoz, F. [CHRU Caen, Laboratoire d' anatomopathologie, Caen, F-14000 (France); Hitier, M. [CHRU Caen, Service d' Otorhinolaryngologie, Caen, F-14000,France (France); Landemore, G. [CHRU Caen, Laboratoire d' anatomopathologie, Caen, F-14000 (France); Philoxène, B. [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); CHRU Caen, Explorations Fonctionnelles, Caen, F-14000 (France); Besnard, S., E-mail: besnard-s@phycog.org [INSERM, ERI27, Caen, F-14000 (France); Univ Caen, Caen, F-14000 (France); CHRU Caen, Explorations Fonctionnelles, Caen, F-14000 (France)

    2012-01-01

    Several animal models of vestibular deficits that mimic the human pathology phenotype have previously been developed to correlate the degree of vestibular injury to cognate vestibular deficits in a time-dependent manner. Sodium arsanilate is one of the most commonly used substances for chemical vestibular lesioning, but it is not well described in the literature. In the present study, we used histological and functional approaches to conduct a detailed exploration of the model of vestibular lesions induced by transtympanic injection of sodium arsanilate in rats. The arsanilate-induced damage was restricted to the vestibular sensory organs without affecting the external ear, the oropharynx, or Scarpa's ganglion. This finding strongly supports the absence of diffusion of arsanilate into the external ear or Eustachian tubes, or through the eighth cranial nerve sheath leading to the brainstem. One of the striking observations of the present study is the complete restructuring of the sensory epithelia into a non sensory epithelial monolayer observed at 3 months after arsanilate application. This atrophy resembles the monolayer epithelia observed postmortem in the vestibular epithelia of patients with a history of lesioned vestibular deficits such as labyrinthectomy, antibiotic treatment, vestibular neuritis, or Ménière's disease. In cases of Ménière's disease, aminoglycosides, and platinum-based chemotherapy, vestibular hair cells are destroyed, regardless of the physiopathological process, as reproduced with the arsanilate model of vestibular lesion. These observations, together with those presented in this study of arsanilate vestibular toxicity, suggest that this atrophy process relies on a common mechanism of degeneration of the sensory epithelia.

  6. Identification of potentially cytotoxic lesions induced by UVA photoactivation of DNA 4-thiothymidine in human cells

    Science.gov (United States)

    Reelfs, Olivier; Macpherson, Peter; Ren, Xiaolin; Xu, Yao-Zhong; Karran, Peter; Young, Antony R.

    2011-01-01

    Photochemotherapy—in which a photosensitizing drug is combined with ultraviolet or visible radiation—has proven therapeutic effectiveness. Existing approaches have drawbacks, however, and there is a clinical need to develop alternatives offering improved target cell selectivity. DNA substitution by 4-thiothymidine (S4TdR) sensitizes cells to killing by ultraviolet A (UVA) radiation. Here, we demonstrate that UVA photoactivation of DNA S4TdR does not generate reactive oxygen or cause direct DNA breakage and is only minimally mutagenic. In an organotypic human skin model, UVA penetration is sufficiently robust to kill S4TdR-photosensitized epidermal cells. We have investigated the DNA lesions responsible for toxicity. Although thymidine is the predominant UVA photoproduct of S4TdR in dilute solution, more complex lesions are formed when S4TdR-containing oligonucleotides are irradiated. One of these, a thietane/S5-(6-4)T:T, is structurally related to the (6-4) pyrimidine:pyrimidone [(6-4) Py:Py] photoproducts induced by UVB/C radiation. These lesions are detectable in DNA from S4TdR/UVA-treated cells and are excised from DNA more efficiently by keratinocytes than by leukaemia cells. UVA irradiation also induces DNA interstrand crosslinking of S4TdR-containing duplex oligonucleotides. Cells defective in repairing (6-4) Py:Py DNA adducts or processing DNA crosslinks are extremely sensitive to S4TdR/UVA indicating that these lesions contribute significantly to S4TdR/UVA cytotoxicity. PMID:21890905

  7. Protective effects of cannabidiol on lesion-induced intervertebral disc degeneration.

    Directory of Open Access Journals (Sweden)

    João W Silveira

    Full Text Available Disc degeneration is a multifactorial process that involves hypoxia, inflammation, neoinnervation, accelerated catabolism, and reduction in water and glycosaminoglycan content. Cannabidiol is the main non-psychotropic component of the Cannabis sativa with protective and anti-inflammatory properties. However, possible therapeutic effects of cannabidiol on intervertebral disc degeneration have not been investigated yet. The present study investigated the effects of cannabidiol intradiscal injection in the coccygeal intervertebral disc degeneration induced by the needle puncture model using magnetic resonance imaging (MRI and histological analyses. Disc injury was induced in the tail of male Wistar rats via a single needle puncture. The discs selected for injury were punctured percutaneously using a 21-gauge needle. MRI and histological evaluation were employed to assess the results. The effects of intradiscal injection of cannabidiol (30, 60 or 120 nmol injected immediately after lesion were analyzed acutely (2 days by MRI. The experimental group that received cannabidiol 120 nmol was resubmitted to MRI examination and then to histological analyses 15 days after lesion/cannabidiol injection. The needle puncture produced a significant disc injury detected both by MRI and histological analyses. Cannabidiol significantly attenuated the effects of disc injury induced by the needle puncture. Considering that cannabidiol presents an extremely safe profile and is currently being used clinically, these results suggest that this compound could be useful in the treatment of intervertebral disc degeneration.

  8. Topical photosan-mediated photodynamic therapy for DMBA-induced hamster buccal pouch early cancer lesions: an in vivo study

    Science.gov (United States)

    Hsu, Yih-Chih; Chang, Walter Hong-Shong; Chang, Junn-Liang; Liu, Kuang-Ting; Chiang, Chun-Pin; Liu, Chung-Ji; Chen, Chih-Ping

    2011-03-01

    Oral cancer has becomes the most prominent cancer disease in recent years in Taiwan. The reason is the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people results in oral cancer becomes the fastest growth incident cancer amongst other major cancer diseases. In previous studies showed that photosan, haematoporphyrin derivative (HPD), has demonstrated effective PDT results on human head and neck disease studies. To avoid the systemic phototoxic effect of photosan, this study was designed to use a topical photosan-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical photosan-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when photosan reached its peak level in the lesional epithelial cells after topical application of photosan gel. We found that photosan reached its peak level in cancerous lesions about 13.5 min after topical application of photosan gel. The cancerous lesions in hamsters were then treated with topical photosan-mediated PDT (fluence rate: 600 mW/cm2; light exposure dose 200 J/cm2) using the portable Lumacare 635 nm fiber-guided light device. Visual examination demonstrated that topical photosan-mediated PDT was an applicable treatment modality for DMBA-induced hamster buccal pouch cancerous lesions.

  9. Combination therapies in adjuvant with topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Hsu, Yih-Chih

    2012-03-01

    In Taiwan, oral cancer has becomes the fastest growth male cancer disease due to the betel nut chewing habit combing with smoking and alcohol-drinking lifestyle of people. In order to eliminate the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 10 to 12 weeks. Cancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when ALA reached its peak level in the lesional epithelial cells after topical application of ALA gel. We found that ALA reached its peak level in precancerous lesions about 2.5 hrs after topical application of ALA gel. The cancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 150 J/cm2 using LED 635 nm fiber-guided light device. Visual examination demonstrated that adjuvant topical ALA -mediated PDT group has shown better therapeutic results in compared to those of non-adjuvant topical ALA-mediated PDT group for DMBA-induced hamster buccal pouch precancerous lesions.

  10. Effects of Tang Mai Kang Capsule on Angioneurotic Lesions in Alloxan-Induced Diabetic Mice

    Institute of Scientific and Technical Information of China (English)

    李华; 王军; 高丽君; 郭永成

    2004-01-01

    The effects of Tang Mai Kang Capsule (糖脉康胶囊) on blood sugar level, gangrene of the tail-tip, pain threshold and learning and memory abilities were investigated in alloxan-induced diabetic mice. The results showed that Tang Mai Kang Capsule could significantly decrease blood sugar level and incidence rate of gangrene of the tail-tip, increase pain threshold, and strengthen learning and memory abilities, suggesting that Tang Mai Kang Capsule functions to decrease blood sugar level and improve the complicated angioneurotic lesions of diabetes.

  11. Protective effect of ginsenoside Re on acute gastric mucosal lesion induced by compound 48/80

    Directory of Open Access Journals (Sweden)

    Sena Lee

    2014-04-01

    Full Text Available The protective effect of ginsenoside Re, isolated from ginseng berry, against acute gastric mucosal lesions was examined in rats with a single intraperitoneal injection of compound 48/80 (C48/80. Ginsenoside Re (20 mg/kg or 100 mg/kg was orally administered 0.5 h prior to C48/80 treatment. Ginsenoside Re dose-dependently prevented gastric mucosal lesion development 3 h after C48/80 treatment. Increases in the activities of myeloperoxidase (MPO; an index of neutrophil infiltration and xanthine oxidase (XO and the content of thiobarbituric acid reactive substances (TBARS; an index of lipid peroxidation and decreases in the contents of hexosamine (a marker of gastric mucus and adherent mucus, which occurred in gastric mucosal tissues after C48/80 treatment, were significantly attenuated by ginsenoside Re. The elevation of Bax expression and the decrease in Bcl2 expression after C48/80 treatment were also attenuated by ginsenoside Re. Ginsenoside Re significantly attenuated all these changes 3 h after C48/80 treatment. These results indicate that orally administered ginsenoside Re protects against C48/80-induced acute gastric mucosal lesions in rats, possibly through its stimulatory action on gastric mucus synthesis and secretion, its inhibitory action on neutrophil infiltration, and enhanced lipid peroxidation in the gastric mucosal tissue.

  12. Effect of probiotics on the development of dimethylhydrazine-induced preneoplastic lesions in the mice colon

    Directory of Open Access Journals (Sweden)

    Juliana Costa Liboredo

    2013-05-01

    Full Text Available PURPOSE: To determine the effect of probiotics on the development of chemically induced (1, 2-dimethylhydrazine colonic preneoplastic lesions, in mice. METHODS: The animals were divided into five groups. The control group was injected with carcinogen alone and the other groups also received probiotics (1- Lactobacillus delbrueckii UFV-H2b20; 2- Bifidobacterium animalis var. lactis Bb12; 3- L. delbrueckii UFV-H2b20 plus B. animalis var. lactis Bb12; and 4- Saccharomyces boulardii administered orally in drinking water throughout fourteen weeks. RESULTS: Consumption of lactobacilli and bifidobacteria alone resulted in a significant reduction of the total number of aberrant crypt foci (55.7% and 45.1%, respectively. Significant reduction in the number of these small foci (3 aberrant crypts crypts had no significant reduction. CONCLUSION: L. delbrueckii UFV-H2b20 and B. animalis var. lactis Bb12 administered alone protect colonic preneoplastic lesions in mice, while the combined treatment of these bacteria and the administration of S.boulardii were not effective in reducing such colonic lesions.

  13. Gastric and intestinal surgery.

    Science.gov (United States)

    Fossum, Theresa W; Hedlund, Cheryl S

    2003-09-01

    Gastric surgery is commonly performed to remove foreign bodies and correct gastric dilatation-volvulus and is less commonly performed to treat gastric ulceration or erosion, neoplasia, and benign gastric outflow obstruction. Intestinal surgery, although commonly performed by veterinarians, should never be considered routine. The most common procedures of the small intestinal tract performed in dogs and cats include enterotomy and resection/anastomosis. Surgery of the large intestine is indicated for lesions causing obstruction, perforations, colonic inertia, or chronic inflammation.

  14. Modulatory effect of fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases in streptozotocin induced diabetic rats.

    Science.gov (United States)

    Kumar, G Suresh; Shetty, A K; Salimath, P V

    2005-06-01

    To elucidate the effect of feeding fenugreek seed mucilage and spent turmeric (10%) on disaccharidases activities, the specific activities of intestinal and renal disaccharidases viz., sucrase, maltase and lactase were measured in streptozotocin induced diabetic rats. Specific activities of intestinal disaccharidases were increased significantly during diabetes and amelioration of these activities during diabetes was clearly visible by supplementing fenugreek seed mucilage and spent turmeric in the diet. However during diabetes renal disaccharidases activities were significantly lower than those in the control rats. Fenugreek seed mucilage and spent turmeric supplementations were beneficial in alleviating the reduction in maltase activity during diabetes, however not much change in the activities of sucrase and lactase was observed upon feeding. This positive influence of feeding fenugreek seed mucilage and spent turmeric on intestinal and renal disaccharidases clearly indicates their beneficial role in the management of diabetes.

  15. The intestinal microbiota determines the colitis‐inducing potential of T‐bet‐deficient Th cells in mice

    Science.gov (United States)

    Zimmermann, Jakob; Durek, Pawel; Kühl, Anja A.; Schattenberg, Florian; Maschmeyer, Patrick; Siracusa, Francesco; Lehmann, Katrin; Westendorf, Kerstin; Weber, Melanie; Riedel, René; Müller, Susann; Radbruch, Andreas

    2017-01-01

    Abstract Conflicting evidence has been provided as to whether induction of intestinal inflammation by adoptive transfer of naïve T cells into Rag −/− mice requires expression of the transcription factor T‑bet by the T cells. Here, we formally show that the intestinal microbiota composition of the Rag −/− recipient determines whether or not T‐bet‐deficient Th cells can induce colitis and we have resolved the differences of the two microbiomes, permissive or non‐permissive to T‐bet‐independent colitis. Our data highlight the dominance of the microbiota over particular T cell differentiation programs in the pathogenesis of chronic intestinal inflammation. PMID:28875499

  16. Protective Role of R-spondin1, an Intestinal Stem Cell Growth Factor, against Radiation-Induced Gastrointestinal Syndrome in Mice

    OpenAIRE

    Bhanja, Payel; Saha, Subhrajit; Kabarriti, Rafi; Liu, Laibin; Roy-Chowdhury, Namita; Roy-Chowdhury, Jayanta; Sellers, Rani S.; Alfieri, Alan A.; Guha, Chandan

    2009-01-01

    Background Radiation-induced gastrointestinal syndrome (RIGS) results from a combination of direct cytocidal effects on intestinal crypt and endothelial cells and subsequent loss of the mucosal barrier, resulting in electrolyte imbalance, diarrhea, weight loss, infection and mortality. Because R-spondin1 (Rspo1) acts as a mitogenic factor for intestinal stem cells, we hypothesized that systemic administration of Rspo1 would amplify the intestinal crypt cells and accelerate the regeneration of...

  17. The role of Wnt/β-catenin signaling in enterocyte turnover during methotrexate-induced intestinal mucositis in a rat.

    Directory of Open Access Journals (Sweden)

    Igor Sukhotnik

    Full Text Available BACKGROUND/AIMS: Intestinal mucositis is a common side-effect in patients who receive aggressive chemotherapy. The Wnt signaling pathway is critical for establishing and maintaining the proliferative compartment of the intestine. In the present study, we tested whether Wnt/β-catenin signaling is involved in methotrexate (MTX-induced intestinal damage in a rat model. METHODS: Non-pretreated and pretreated with MTX Caco-2 cells were evaluated for cell proliferation and apoptosis using FACS analysis. Adult rats were divided into three experimental groups: Control rats; MTX-2 animals were treated with a single dose of MTX given IP and were sacrificed on day 2, and MTX-4 rats were treated with MTX similar to group B and were sacrificed on day 4. Intestinal mucosal damage, mucosal structural changes, enterocyte proliferation, and enterocyte apoptosis were measured at sacrifice. Real Time PCR and Western blot was used to determine the level of Wnt/β-catenin related genes and protein expression. RESULTS: In the vitro experiment, treatment with MTX resulted in marked decrease in early cell proliferation rates following by a 17-fold increase in late cell proliferation rates compared to early proliferation. Treatment with MTX resulted in a significant increase in early and late apoptosis compared to Caco-2 untreated cells. In the vivo experiment, MTX-2 and MTX-4 rats demonstrated intestinal mucosal hypoplasia. MTX-2 rats demonstrated a significant decrease in FRZ-2, Wnt 3A Wnt 5A, β-catenin, c-myc mRNA expression and a significant decrease in β-catenin and Akt protein levels compared to control animals. Four days following MTX administration, rats demonstrated a trend toward a restoration of Wnt/β-catenin signaling especially in ileum. CONCLUSIONS: Wnt/β-catenin signaling is involved in enterocyte turnover during MTX-induced intestinal mucositis in a rat.

  18. Fructose-induced increases in expression of intestinal fructolytic and gluconeogenic genes are regulated by GLUT5 and KHK

    Science.gov (United States)

    Patel, Chirag; Douard, Veronique; Yu, Shiyan; Tharabenjasin, Phuntila; Gao, Nan

    2015-01-01

    Marked increases in fructose consumption have been tightly linked to metabolic diseases. One-third of ingested fructose is metabolized in the small intestine, but the underlying mechanisms regulating expression of fructose-metabolizing enzymes are not known. We used genetic mouse models to test the hypothesis that fructose absorption via glucose transporter protein, member 5 (GLUT5), metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein in brain 11a (Rab11a)-dependent endosomes are required for the regulation of intestinal fructolytic and gluconeogenic enzymes. Fructose feeding increased the intestinal mRNA and protein expression of these enzymes in the small intestine of adult wild-type (WT) mice compared with those gavage fed with lysine or glucose. Fructose did not increase expression of these enzymes in the GLUT5 knockout (KO) mice. Blocking intracellular fructose metabolism by KHK ablation also prevented fructose-induced upregulation. Glycolytic hexokinase I expression was similar between WT and GLUT5- or KHK-KO mice and did not vary with feeding solution. Gavage feeding with the fructose-specific metabolite glyceraldehyde did not increase enzyme expression, suggesting that signaling occurs before the hydrolysis of fructose to three-carbon compounds. Impeding GLUT5 trafficking to the apical membrane using intestinal epithelial cell-specific Rab11a-KO mice impaired fructose-induced upregulation. KHK expression was uniformly distributed along the villus but was localized mainly in the basal region of the cytosol of enterocytes. The feedforward upregulation of fructolytic and gluconeogenic enzymes specifically requires GLUT5 and KHK and may proactively enhance the intestine's ability to process anticipated increases in dietary fructose concentrations. PMID:26084694

  19. Lung Function Impairment in Relation to Asbestos-Induced Pleural Lesions with Reference to the Extent of the Lesions and the Initial Parenchymal Fibrosis.

    Czech Academy of Sciences Publication Activity Database

    Lebedová, J.; Dlouhá, B.; Rychlá, L.; Neuwirth, J.; Brabec, Marek; Pelclová, D.; Fenclová, Z.

    2003-01-01

    Roč. 29, č. 5 (2003), s. 388-395 ISSN 0355-3140 Source of funding: V - iné verejné zdroje Keywords : asbestos exposure * asbestos-induced pleural lesion * asbestosis * lung function impairmentp * arenchymal fibrosis * pleural change * pleural thickening * ventilation impairment Subject RIV: BB - Applied Statistics, Operational Research Impact factor: 1.816, year: 2003 http://www.jstor.org/stable/40967314

  20. The Protective Role of Ginkgo Biloba against Radiation Induced Injury on Rat Gastro-intestinal Tract

    International Nuclear Information System (INIS)

    El-Ghazaly, M.A.; Gharib, O.A.; El-Sheikh, M.M.; Khayyal, M.T.

    2015-01-01

    Ginkgo Biloba extract (EGb 761) is an antioxidant substance exhibits a wide variety of biological activities. The present study was performed to evaluate oxidative stress and inflammatory parameters of gastrointestinal injury induced by exposing rats to acute doses of γ-rays and the potential value of EGb 761 in preventing changes in these parameters. Male albino rats were treated orally with the extract in a dose of 100 mg/ kg for 7 successive days before whole body exposure to acute radiation levels of 2 and 6 Gray (Gy). Control groups were run concurrently. The rats were sacrificed 3 days after irradiation. Various inflammatory mediators and biochemical parameters were determined in the stomach and intestine. Both tissues were also examined histopathologically. Exposure to radiation led to dose dependent changes in the level of oxidative stress biomarkers (elevation of thiobarbituric acid reactive substance (TBARS) and nitrite associated with a glutathione (GSH) decrease as well as in the level of inflammatory parameters (elevation of Tumour necrosis factorα (TNF-α) and myeloperoxidase (MPO) associated with depletion of prostaglandin E 2 (PGE 2 ). Pre-treatment with EGb 761 protected against the changes in both oxidative stress biomarkers and inflammatory mediators. EGb 761 exerted a protective effect against the radiation induced gastrointestinal damage, possibly through its anti-inflammatory and anti-oxidant properties.

  1. Effect of radiomodifying agents on the ratios of X-ray-induced lesions in cellular DNA: use in lethal lesion determination

    International Nuclear Information System (INIS)

    Radford, I.R.

    1986-01-01

    The effect of three radiomodifying agents, cysteamine, hyperthermia, and hypoxia, on the induction of the major classes of X-ray-induced DNA lesions, was studied using mouse L cells and Chinese hamster V79 cells. The use of filter elution techniques allowed most of these studies to be conducted at X-ray doses within the survival-curve range. Cysteamine was found to protect against DNA single-strand breakage (ssb), DNA base damage, and DNA-protein crosslinkage. Hyperthermia had no effect on the level of DNA ssb or DNA base damage, but in L cells (but not in V79 cells) it increased the level of DNA-protein crosslinkage relative to DNA ssb. Hypoxia protected against DNA ssb, had no significant effect on the level of DNA base damage, and enhanced the level of DNA-protein crosslinkage relative to DNA ssb. These results support the previous suggestion that the X-ray-induced lethal lesion is DNA double-strand breakage. Implications of these findings for the mechanisms of formation of X-ray-induced DNA lesions are also discussed. (author)

  2. Protective Effect of Royal Jelly against Phenylhydrazine-induced Histological Injuries of Small Intestine of Mice: Morphometric Analyses

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    Hojat Anbara

    2016-01-01

    Full Text Available Background and Objectives: Phenylhydrazine (PHZ, as a known hemolytic agent, causes toxicity in different tissues at various levels. The aim of the current study was to examine the possible protective effects of royal jelly (RJ against PHZ-induced histological injuries of small intestine in mice.   Methods: In this experimental study, adult male mice were randomly divided into four groups of 8 mice each. PHZ was administered intraperitoneally to two groups of mice (at a dose of 60mg/kg every 48 hours for 35 days. One of the groups received RJ (100mg/kg orally 4 hours before PHZ administration. The third group only received RJ, and the forth group was considered as control. Twenty-four hours after the last treatment, different segments of small intestine were dissected out, then histological sections were prepared and quantitative morphometric assessments were performed. To compare the groups, one-way ANOVA and multiple comparative Tukey tests were used. The significance level was considered to be p<0.05.   Results: In this study, PHZ caused significant decreases in depth of duodenal crypts, distribution rate of the goblet cells in ileal villi, width of duodenal and jejunal villi, and height of villi in all three segments of small intestine. Co-administration of RJ partially improved the changes in the above parameters.   Conclusion: From results of this study, it seems that RJ as a free radical scavenger could reduce PHZ-induced intestinal toxicity in mouse.

  3. Radiation-induced hyperproliferation of intestinal crypts results in elevated genome instability with inactive p53-related genomic surveillance.

    Science.gov (United States)

    Zhou, Xin; Ma, Xiaofei; Wang, Zhenhua; Sun, Chao; Wang, Yupei; He, Yang; Zhang, Hong

    2015-12-15

    Radiation-induced hyperproliferation of intestinal crypts is well documented, but its potential tumorigenic effects remain elusive. Here we aim to determine the genomic surveillance process during crypt hyperproliferation, and its consequential outcome after ionizing radiation. Crypt regeneration in the intestine was induced by a single dose of 12Gy abdominal irradiation. γ-H2AX, 53BP1 and DNA-PKcs were used as DNA repair surrogates to investigate the inherent ability of intestinal crypt cells to recognize and repair double-strand breaks. Ki67 staining and the 5-bromo-2'-deoxyuridine incorporation assay were used to study patterns of cell proliferation in regenerating crypts. Staining for ATM, p53, Chk1 and Chk2 was performed to study checkpoint activation and release. Apoptosis was evaluated through H&E staining and terminal deoxynucleotidyl transferase (dUTP) nick-end labeling. The ATM-p53 pathway was immediately activated after irradiation. A second wave of DSBs in crypt cells was observed in regenerating crypts, accompanied with significantly increased chromosomal bridges. The p53-related genomic surveillance pathway was not active during the regeneration phase despite DSBs and chromosomal bridges in the cells of regenerating crypts. Non-homologous end joining (NHEJ) DSBs repair was involved in the DSBs repair process, as indicated by p-DNA-PKcs staining. Intestinal crypt cells retained hyperproliferation with inactive p53-related genomic surveillance system. NHEJ was involved in the resultant genomic instability during hyperproliferation. Copyright © 2015 Elsevier Inc. All rights reserved.

  4. An orally active Cannabis extract with high content in cannabidiol attenuates chemical induced intestinal inflammation and hypermotility in the mouse

    Directory of Open Access Journals (Sweden)

    Ester Pagano

    2016-10-01

    Full Text Available Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD, here named CBD BDS for CBD botanical drug substance, on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS. Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol. The amounts of CBD in the colon, brain and liver after the oral treatments were measured by HPLC coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion or orally (only at one dose. In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  5. Interferon-γ induces expression of MHC class II on intestinal epithelial cells and protects mice from colitis.

    Directory of Open Access Journals (Sweden)

    Christoph Thelemann

    Full Text Available Immune responses against intestinal microbiota contribute to the pathogenesis of inflammatory bowel diseases (IBD and involve CD4(+ T cells, which are activated by major histocompatibility complex class II (MHCII molecules on antigen-presenting cells (APCs. However, it is largely unexplored how inflammation-induced MHCII expression by intestinal epithelial cells (IEC affects CD4(+ T cell-mediated immunity or tolerance induction in vivo. Here, we investigated how epithelial MHCII expression is induced and how a deficiency in inducible epithelial MHCII expression alters susceptibility to colitis and the outcome of colon-specific immune responses. Colitis was induced in mice that lacked inducible expression of MHCII molecules on all nonhematopoietic cells, or specifically on IECs, by continuous infection with Helicobacter hepaticus and administration of interleukin (IL-10 receptor-blocking antibodies (anti-IL10R mAb. To assess the role of interferon (IFN-γ in inducing epithelial MHCII expression, the T cell adoptive transfer model of colitis was used. Abrogation of MHCII expression by nonhematopoietic cells or IECs induces colitis associated with increased colonic frequencies of innate immune cells and expression of proinflammatory cytokines. CD4(+ T-helper type (Th1 cells - but not group 3 innate lymphoid cells (ILCs or Th17 cells - are elevated, resulting in an unfavourably altered ratio between CD4(+ T cells and forkhead box P3 (FoxP3(+ regulatory T (Treg cells. IFN-γ produced mainly by CD4(+ T cells is required to upregulate MHCII expression by IECs. These results suggest that, in addition to its proinflammatory roles, IFN-γ exerts a critical anti-inflammatory function in the intestine which protects against colitis by inducing MHCII expression on IECs. This may explain the failure of anti-IFN-γ treatment to induce remission in IBD patients, despite the association of elevated IFN-γ and IBD.

  6. Nephroprotective and anti-inflammatory effects of aqueous extract of Melissa officinalis L. on acetaminophen-induced and pleurisy-induced lesions in rats

    Directory of Open Access Journals (Sweden)

    Denise Pereira Müzell

    2013-06-01

    Full Text Available This study assessed the bioactive properties of an aqueous extract of M. officinalis for its anti-inflammatory activity and its protection against hepatic and renal lesions induced by acetaminophen (APAP. Animals pre-treated with the crude extract in pleurisy induced by carrageenan showed a reduction in the amounts of exudate, in the numbers of leukocytes and polymorphonuclear cells. Intragastric administration of the extract for seven days prior to the APAP-induced lesion showed no protective effect on the liver. The treatment with the extract induced an increase of serum aspartate aminotransferase, indicating a rise of toxicity. Contrarily, the same treatment reduced the APAP induced lesion in kidney, with respect to ν-glutamyltransferase. The results suggested that the extract was not hepatoprotective and could lead to an increase in the lesions induced by the APAP. On the other hand, the extract was nephroprotective against the lesions induced by the APAP and showed an anti-inflammatory effect on pleurisy carrageenan-induced.

  7. The inhibitory effect of tiamulin on high K(+)-induced contraction in guinea pig intestinal smooth muscle.

    Science.gov (United States)

    Nakajyo, S; Fukui, T; Hara, Y; Shimizu, K; Urakawa, N

    1991-12-01

    Tiamulin with an IC50 of 1.7 x 10(-6) M inhibited both the rapid and sustained contractions induced by hyperosmotically added 60 mM K+ (Hyper 60 K+) without changing the membrane potential in the intestinal muscle. Tiamulin inhibition (2 x 10(-6)-2 x 10(-5) M) of the Ca(2+)-induced contraction in depolarized muscle was competitively antagonized by raising external Ca2+. Tiamulin (2 x 10(-5) M) slightly affected the Hyper 60 K(+)-induced phasic contraction under hypoxia and the carbachol-induced phasic contraction. Moreover, tiamulin (2 x 10(-5) M) inhibited the Hyper 60 K(+)-induced contraction with decreasing [Ca2+]cyt level. Although the inhibitory effect of 10(-7)-10(-5) M monesin, an inhibitor of mitochondrial respiration, on the Hyper 60 K(+)-induced contraction was reduced under hypoxia, the effect of tiamulin (2 x 10(-7)-2 x 10(-4) M) was not modified. Tiamulin changed neither the intracellular Na+ and K+ content of the depolarized muscle nor the Ca(2+)-induced contraction in the chemically skinned preparations. These results suggest that the inhibitory action of tiamulin on the Hyper 60 K(+)-induced tonic contraction is possibly due to the competitive inhibition of Ca2+ entry through the voltage-dependent Ca2+ channel of the intestinal smooth muscle cell.

  8. Arginyl-glutamine dipeptide or docosahexaenoic acid attenuates hyperoxia-induced small intestinal injury in neonatal mice.

    Science.gov (United States)

    Li, Nan; Ma, Liya; Liu, Xueyan; Shaw, Lynn; Li Calzi, Sergio; Grant, Maria B; Neu, Josef

    2012-04-01

    Supplementation studies of glutamine, arginine, and docosahexaenoic acid (DHA) have established the safety of each of these nutrients in neonates; however, the potential for a more stable and soluble dipeptide, arginyl-glutamine (Arg-Gln) or DHA with anti-inflammatory properties, to exert benefits on hyperoxia-induced intestinal injury has not been investigated. Arg-Gln dipeptide has been shown to prevent retinal damage in a rodent model of oxygen-induced injury. The objective of the present study was to investigate whether Arg-Gln dipeptide or DHA could also attenuate markers of injury and inflammation to the small intestine in this same model. Seven-day-old mouse pups were placed with their dams in 75% oxygen for 5 days. After 5 days of hyperoxic exposure (P7-P12), pups were removed from hyperoxia and allowed to recover in atmospheric conditions for 5 days (P12-P17). Mouse pups received Arg-Gln (5g·kg·day) or DHA (5g·kg·day) or vehicle orally started on P12 through P17. Distal small intestine (DSI) histologic changes, myeloperoxidase (MPO), lactate dehydrogenase (LDH), inflammatory cytokines, and tissue apoptosis were evaluated. Hyperoxic mice showed a greater distortion of overall villus structure and with higher injury score (PDHA supplementation groups were more similar to the room air control group. Supplementation of Arg-Gln or DHA reduced hyperoxia-induced MPO activity (PDHA returned LDH activity to the levels of control. Hyperoxia induced apoptotic cell death in DSIs, and both Arg-Gln and DHA reversed this effect (PDHA may limit some inflammatory and apoptotic processes involved in hyperoxic-induced intestinal injury in neonatal mice.

  9. Intestinal CREBH overexpression prevents high-cholesterol diet-induced hypercholesterolemia by reducing Npc1l1 expression

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    Takuya Kikuchi

    2016-11-01

    Conclusion: Intestinal CREBH regulates dietary cholesterol flow from the small intestine by controlling the expression of multiple intestinal transporters. We propose that intestinal CREBH could be a therapeutic target for hypercholesterolemia.

  10. [Terbinafine : Drug-induced lupus erythematodes and triggering of psoriatic skin lesions].

    Science.gov (United States)

    Mayser, P

    2016-09-01

    Based on the technical information that oral terbinafine must be used with caution in patients with pre-existing psoriasis or lupus erythematosus, the literature was summarized. Terbinafine belongs to the drugs able to induce subcutaneous lupus erythematosus (SCLE)-with a relatively high risk. The clinical picture of terbinafine-induced SCLE may be highly variable and can also include erythema exsudativum multiforme-like or bullous lesions. Thus, differentiation of terbinafine-induced Stevens-Johnson syndrome or toxic epidermal necrolysis may be difficult. Therefore, terbinafine should be prescribed with caution in patients who show light sensitivity, arthralgias, positive antinuclear antibodies or have a history of SLE or SCLE. Case reports include wide-spread, but mostly nonlife-threatening courses, which did not require systemic therapy with steroids or antimalarials in every case. Terbinafine is also able to induce or to aggravate psoriasis. The latency period seems to be rather short (Terbinafine therefore is not first choice if a systemic therapy with antimycotics is indicated in a patient with psoriasis or psoriatic diathesis. Azole derivatives according to the guidelines may be used as an alternative.

  11. The role of metabolism in Diclofenac-induced intestinal toxicity in human ex vivo

    NARCIS (Netherlands)

    Niu, Xiaoyu; Makkinje, Miriam; de Graaf, Inge; Groothuis, Genoveva

    2012-01-01

    The use of Diclofenac (DCF: 2-(2,6-dichloranilino) phenyl acetic acid ), a non-steroidal anti-inflammatory drug is associated with severe gastro-intestinal side-effects. In vivo rat studies suggest that reactive metabolites of DCF, produced by the liver, play an important role in the intestinal

  12. Consequences of Mrp2 deficiency for diclofenac-induced toxicity in rat intestine in vitro

    NARCIS (Netherlands)

    Niu, Xiaoyu; van de Vegte, Dennis; Makkinje, Miriam; de Graaf, Inge; Groothuis, Genoveva

    Diclofenac (DCF), a widely used non-steroidal anti-inflammatory drug (NSAID), is associated with high prevalence of severe intestinal side-effects. The reactive metabolite diclofenac acylglucuronide (DAG) formed in the liver, and transported by bile into the intestine was reported to be involved in

  13. Prickly pear cactus (Opuntia ficus indica var. saboten) protects against stress-induced acute gastric lesions in rats.

    Science.gov (United States)

    Kim, Seung Hyun; Jeon, Byung Ju; Kim, Dae Hyun; Kim, Tae Il; Lee, Hee Kyoung; Han, Dae Seob; Lee, Jong-Hwan; Kim, Tae Bum; Kim, Jung Wha; Sung, Sang Hyun

    2012-11-01

    The protective activity of prickly pear cactus (Opuntia ficus indica var. saboten) fruit juice and its main constituent, betanin, were evaluated against stress-induced acute gastric lesions in rats. After 6 h of water immersion restraint stress (WIRS), gastric mucosal lesions with bleeding were induced in Sprague-Dawley rats. Pretreatment of a lyophilized powder containing O. ficus indica var. saboten fruit juice and maltodextrin (OFSM) and betanin significantly reduced stress lesions (800-1600 mg/kg). Both OFSM and betanin effectively prevented the decrease in gastric mucus content as detected by alcian blue staining. In addition, OFSM significantly suppressed WIRS-induced increases in the level of gastric mucosal tumor necrosis factor-α and myeloperoxidase (MPO). Betanin alone was only effective in decreasing MPO. These results revealed the protective activity of OFSM against stress-induced acute gastric lesions and that betanin may contribute to OFSM's gastric protective activity, at least in part. When OFSM and betanin were taken together, OFSM exerted gastroprotective activity against stress-induced gastric lesions by maintaining gastric mucus, which might be related to the attenuation of MPO-mediated damage and proinflammatory cytokine production.

  14. Attenuation of radiation- and drug-induced conditioned taste aversions following area postrema lesions in the rat

    International Nuclear Information System (INIS)

    Rabin, B.M.; Hunt, W.A.; Lee, J.

    1983-01-01

    The effects of lesions of the area postrema on the acquisition of radiation- and drug-induced (histamine and lithium chloride) conditioned taste aversions were investigated. The results indicated that area postrema lesions caused a significant attenuation of the aversion produced by pairing a novel sucrose solution with radiation (100 rad) or drug injection. Further, the area postrema lesions produced a similar level of attenuation of the taste aversion in all three treatment conditions. The results are discussed in terms of the implications of this finding for defining the mechanisms by which exposure to ionizing radiation can lead to the acquisition of a conditioned taste aversion

  15. Electroacupuncture Inhibits Inflammation Reaction by Upregulating Vasoactive Intestinal Peptide in Rats with Adjuvant-Induced Arthritis

    Directory of Open Access Journals (Sweden)

    Tian-Feng He

    2011-01-01

    Full Text Available Acupuncture is emerging as an alternative therapy for rheumatoid arthritis (RA. However, the molecular mechanism underlying this beneficial effect of acupuncture has not been fully understood. Here, we demonstrated that electroacupuncture at acupoints Zusanli (ST36, Xuanzhong (GB39; and Shenshu (BL23 markedly decreased the paw swelling and the histologic scores of inflammation in the synovial tissue, and reduced the body weight loss in an adjuvant-induced arthritis rat model. However, the electrical stimulation at nonacupoint did not produce any beneficial effects against the experimental arthritis. Most interestingly, the electroacupuncture treatment resulted in an enhanced immunostaining for vasoactive intestinal peptide (VIP, a potent anti-inflammatory neuropeptide, in the synovial tissue. Moreover, the VIP-immunostaining intensity was significantly negatively correlated with the scores of inflammation in the synovial tissue (r=−0.483, P=.0026. In conclusion, these findings suggest that electroacupuncture may offer therapeutic benefits for the treatment of RA, at least partially through the induction of VIP expression.

  16. Modulation of chromatin remodelling induced by the freshwater cyanotoxin cylindrospermopsin in human intestinal caco-2 cells.

    Directory of Open Access Journals (Sweden)

    Antoine Huguet

    Full Text Available Cylindrospermopsin (CYN is a cyanotoxin that has been recognised as an emerging potential public health risk. Although CYN toxicity has been demonstrated, the mechanisms involved have not been fully characterised. To identify some key pathways related to this toxicity, we studied the transcriptomic profile of human intestinal Caco-2 cells exposed to a sub-toxic concentration of CYN (1.6 µM for 24hrs using a non-targeted approach. CYN was shown to modulate different biological functions which were related to growth arrest (with down-regulation of cdkn1a and uhrf1 genes, and DNA recombination and repair (with up-regulation of aptx and pms2 genes. Our main results reported an increased expression of some histone-modifying enzymes (histone acetyl and methyltransferases MYST1, KAT5 and EHMT2 involved in chromatin remodelling, which is essential for initiating transcription. We also detected greater levels of acetylated histone H2A (Lys5 and dimethylated histone H3 (Lys4, two products of these enzymes. In conclusion, CYN overexpressed proteins involved in DNA damage repair and transcription, including modifications of nucleosomal histones. Our results highlighted some new cell processes induced by CYN.

  17. Pre-existing Periapical Inflammatory Condition Exacerbates Tooth Extraction–induced BRONJ Lesions in Mice

    Science.gov (United States)

    Song, Minju; Alshaikh, Abdullah; Kim, Terresa; Kim, Sol; Dang, Michelle; Mehrazarin, Shebli; Shin, Ki-Hyuk; Kang, Mo; Park, No-Hee; Kim, Reuben H.

    2016-01-01

    Introduction Surgical interventions such as tooth extraction increase a chance of developing osteonecrosis of the jaw (ONJ) in patients receiving bisphosphonates (BPs) for treatment of bone-related diseases. Tooth extraction is often performed to eliminate pre-existing pathological inflammatory conditions that make the tooth unsalvageable; however, the role of such conditions on bisphosphonate-related ONJ (BRONJ) development following tooth extraction is not clearly defined. Here, we examined the effects of periapical periodontitis on tooth extraction-induced BRONJ development in mice. Methods Periapical periodontitis was induced by exposing the pulp of the maxillary first molar for 3 weeks in C57/BL6 mice that were intravenously administered with BP. The same tooth was extracted, and after 3 additional weeks, the mice were harvested for histological, histomorphometric, and histochemical staining analyses. Results Pulp exposure induced periapical radiolucency as demonstrated by increased inflammatory cells, TRAP+ osteoclasts, and bone resorption. When BP was administered, pulp exposure did not induce apical bone resorption despite the presence of inflammatory cells and TRAP+ osteoclasts. While tooth extraction alone induced BRONJ lesions, pulp exposure further increased tooth extraction-induced BRONJ development as demonstrated by the presence of more bone necrosis. Conclusion Our study demonstrates that pre-existing pathological inflammatory condition such as periapical periodontitis is a predisposing factor that may exacerbate BRONJ development following tooth extraction. Our study further provides a clinical implication whereby periapical periodontitis should be controlled before performing tooth extraction in BP-users in order to reduce the risk of developing BRONJ. PMID:27637460

  18. Soybean β-conglycinin induces inflammation and oxidation and causes dysfunction of intestinal digestion and absorption in fish.

    Directory of Open Access Journals (Sweden)

    Jin-Xiu Zhang

    Full Text Available β-Conglycinin has been identified as one of the major feed allergens. However, studies of β-conglycinin on fish are scarce. This study investigated the effects of β-conglycinin on the growth, digestive and absorptive ability, inflammatory response, oxidative status and gene expression of juvenile Jian carp (Cyprinus carpio var. Jian in vivo and their enterocytes in vitro. The results indicated that the specific growth rate (SGR, feed intake, and feed efficiency were reduced by β-conglycinin. In addition, activities of trypsin, chymotrypsin, lipase, creatine kinase, Na(+,K(+-ATPase and alkaline phosphatase in the intestine showed similar tendencies. The protein content of the hepatopancreas and intestines, and the weight and length of the intestines were all reduced by β-conglycinin. β-Conglycinin increased lipid and protein oxidation in the detected tissues and cells. However, β-conglycinin decreased superoxide dismutase (SOD, catalase (CAT, glutathione-S-transferase (GST, glutathione peroxidase (GPx and glutathione reductase (GR activities and glutathione (GSH content in the intestine and enterocytes. Similar antioxidant activity in the hepatopancreas was observed, except for GST. The expression of target of rapamycin (TOR gene was reduced by β-conglycinin. Furthermore, mRNA levels of interleukin-8 (IL-8, tumor necrosis factor-α (TNF-α, and transforming growth factor-β (TGF-β genes were increased by β-conglycinin. However, β-conglycinin increased CuZnSOD, MnSOD, CAT, and GPx1b gene expression. In conclusion, this study indicates that β-conglycinin induces inflammation and oxidation, and causes dysfunction of intestinal digestion and absorption in fish, and finally reduces fish growth. The results of this study provide some information to the mechanism of β-conglycinin-induced negative effects.

  19. An orally active Cannabis extract with high content in cannabidiol attenuates chemical induced intestinal inflammation and hypermotility in the mouse

    OpenAIRE

    Ester Pagano; Raffaele Capasso; Fabiana Piscitelli; Barbara Romano; Olga Alessandra Parisi; Stefania Finizio; Anna Lauritano; Vincenzo Di Marzo; Angelo A Izzo; Francesca Borrelli

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for CBD botanical drug substance, on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was ev...

  20. Rifaximin-extended intestinal release induces remission in patients with moderately active Crohn's disease.

    Science.gov (United States)

    Prantera, Cosimo; Lochs, Herbert; Grimaldi, Maria; Danese, Silvio; Scribano, Maria Lia; Gionchetti, Paolo

    2012-03-01

    Bacteria might be involved in the development and persistence of inflammation in patients with Crohn's disease (CD), and antibiotics could be used in therapy. We performed a clinical phase 2 trial to determine whether a gastroresistant formulation of rifaximin (extended intestinal release [EIR]) induced remission in patients with moderately active CD. We performed a multicenter, randomized, double-blind trial of the efficacy and safety of 400, 800, and 1200 mg rifaximin-EIR, given twice daily to 402 patients with moderately active CD for 12 weeks. Data from patients given rifaximin-EIR were compared with those from individuals given placebo, and collected during a 12-week follow-up period. The primary end point was remission (Crohn's Disease Activity Index <150) at the end of the treatment period. At the end of the 12-week treatment period, 62% of patients who received the 800-mg dosage of rifaximin-EIR (61 of 98) were in remission, compared with 43% of patients who received placebo (43 of 101) (P = .005). A difference was maintained throughout the 12-week follow-up period (45% [40 of 89] vs 29% [28 of 98]; P = .02). Remission was achieved by 54% (56 of 104) and 47% (47 of 99) of the patients given the 400-mg and 1200-mg dosages of rifaximin-EIR, respectively; these rates did not differ from those of placebo. Patients given the 400-mg and 800-mg dosages of rifaximin-EIR had low rates of withdrawal from the study because of adverse events; rates were significantly higher among patients given the 1200-mg dosage (16% [16 of 99]). Administration of 800 mg rifaximin-EIR twice daily for 12 weeks induced remission with few adverse events in patients with moderately active CD. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

  1. Neural control of locomotion and training-induced plasticity after spinal and cerebral lesions.

    Science.gov (United States)

    Knikou, Maria

    2010-10-01

    Standing and walking require a plethora of sensorimotor interactions that occur throughout the nervous system. Sensory afferent feedback plays a crucial role in the rhythmical muscle activation pattern, as it affects through spinal reflex circuits the spinal neuronal networks responsible for inducing and maintaining rhythmicity, drives short-term and long-term re-organization of the brain and spinal cord circuits, and contributes to recovery of walking after locomotor training. Therefore, spinal circuits integrating sensory signals are adjustable networks with learning capabilities. In this review, I will synthesize the mechanisms underlying phase-dependent modulation of spinal reflexes in healthy humans as well as those with spinal or cerebral lesions along with findings on afferent regulation of spinal reflexes and central pattern generator in reduced animal preparations. Recovery of walking after locomotor training has been documented in numerous studies but the re-organization of spinal interneuronal and cortical circuits need to be further explored at cellular and physiological levels. For maximizing sensorimotor recovery in people with spinal or cerebral lesions, a multidisciplinary approach (rehabilitation, pharmacology, and electrical stimulation) delivered during various sensorimotor constraints is needed. Copyright 2010 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

  2. Radiation-induced osteochondroma-like lesion in young rat radius

    International Nuclear Information System (INIS)

    Delgado, E.; Rodriguez, J.I.; Serrada, A.; Tellez, M.; Paniagua, R.

    1985-01-01

    To investigate the effects of radiation on the perichondrial groove of Ranvier in osteochondroma development, the external surface of the distal growth plate of the radius in both forelimbs of 30 ten-day-old rats was exposed to a single low dose of radiation (150 r), which was focused on the perichondrial groove. This induced the formation of a chondrocyte nest at the proximal external edge of the growth plate (five to nine days after irradiation). With advancing longitudinal growth of the bone, the chondrocyte nest occupied a diaphyseal position. At nine to 11 days the chondrocyte nest underwent endochondral ossification. At 13-15 days, this osteochondroma-like lesion began to regress with the disappearance of the chondrocyte nest. After 19-21 days, only an irregularly thickened cortical bone remains at the osteochondroma site. Although the possible role of the growth plate subjacent to the irradiated perichondrial groove must be taken into account, the continuity between the perichondrial groove and the osteochondroma, which is separated from the growth plate by the periosteal ring (bone bark), suggests that the perichondrial groove was involved in osteochondroma-like lesion development

  3. Radiological protection optimization derived from radiation induced lesions in interventional cardiology finding

    International Nuclear Information System (INIS)

    Vano, E.; Arranz, L.; Sastre, J.M.; Ferrer, N.

    1997-01-01

    Interventional Cardiology is one of the specialties in which patients are submitted to the greatest radiation doses with x ray systems used for diagnostic purposes and then, it is also a specialty of high occupational radiation risk. In the last years, several cases of radiation induced lesions produced on patients derived of new complex interventional procedures have been described. As consequence, different rules for avoiding this kind of incidents have been recommended by International Organisations and regulatory Bodies. Nevertheless it has been devoted relatively few attention to the evaluation of the occupational risks that inevitably are also high in these facilities. In this work, some cases of radioinduced skin lesions produced on patients submitted to cardiac ablation procedures are described. Radiological protection considerations of interest for the regulatory Bodies are made, that permit to minimize the probability of these incidents, in what to the X-rays equipment is referred as well as to the operation procedures and level of radiation protection training of the medical specialists. (author)

  4. Deregulated Lipid Sensing by Intestinal CD36 in Diet-Induced Hyperinsulinemic Obese Mouse Model.

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    Marjorie Buttet

    Full Text Available The metabolic syndrome (MetS greatly increases risk of cardiovascular disease and diabetes and is generally associated with abnormally elevated postprandial triglyceride levels. We evaluated intestinal synthesis of triglyceride-rich lipoproteins (TRL in a mouse model of the MetS obtained by feeding a palm oil-rich high fat diet (HFD. By contrast to control mice, MetS mice secreted two populations of TRL. If the smaller size population represented 44% of total particles in the beginning of intestinal lipid absorption in MetS mice, it accounted for only 17% after 4 h due to the secretion of larger size TRL. The MetS mice displayed accentuated postprandial hypertriglyceridemia up to 3 h due to a defective TRL clearance. These alterations reflected a delay in lipid induction of genes for key proteins of TRL formation (MTP, L-FABP and blood clearance (ApoC2. These abnormalities associated with blunted lipid sensing by CD36, which is normally required to optimize jejunal formation of large TRL. In MetS mice CD36 was not downregulated by lipid in contrast to control mice. Treatment of controls with the proteosomal inhibitor MG132, which prevented CD36 downregulation, resulted in blunted lipid-induction of MTP, L-FABP and ApoC2 gene expression, as in MetS mice. Absence of CD36 sensing was due to the hyperinsulinemia in MetS mice. Acute insulin treatment of controls before lipid administration abolished CD36 downregulation, lipid-induction of TRL genes and reduced postprandial triglycerides (TG, while streptozotocin-treatment of MetS mice restored lipid-induced CD36 degradation and TG secretion. In vitro, insulin treatment abolished CD36-mediated up-regulation of MTP in Caco-2 cells. In conclusion, HFD treatment impairs TRL formation in early stage of lipid absorption via insulin-mediated inhibition of CD36 lipid sensing. This impairment results in production of smaller TRL that are cleared slowly from the circulation, which might contribute to the

  5. Role of serotonin in the intestinal mucosal epithelium barrier in weaning mice undergoing stress-induced diarrhea.

    Science.gov (United States)

    Dong, Yulan; Wang, Zixu; Qin, Zhuoming; Cao, Jing; Chen, Yaoxing

    2018-02-01

    Stress-induced diarrhea is a frequent and challenging threat to humans and domestic animals. Serotonin (5-HT) has been shown to be involved in the pathological process of stress-induced diarrhea. However, the role of 5-HT in stress-induced diarrhea remains unclear. A stress-induced diarrhea model was established in 21-day-old ICR weaning mice through an intragastric administration of 0.25 mL of 0.4 g/mL folium sennae and restraint of the hind legs with adhesive tape for 4 h to determine whether 5-HT regulates the mucosal barrier to cause diarrhea. Mice with decreased levels of 5-HT were pretreated with an intraperitoneal injection of 300 mg/kg p-chlorophenylalanine (PCPA), a 5-HT synthesis inhibitor. After 5 days of treatment, the stress level, body weight and intestinal mucosal morphology indexes were measured. Compared to the controls, the mice with stress-induced diarrhea displayed a stress reaction, with increased corticosterone levels, as well as increased 5-HT-positive cells. However, the mice with stress-induced diarrhea exhibited decreased body weights, villus height to crypt depth ratios (V/C), and Occludin and Claudin1 expression. The PCPA injection reversed these effects in mice with different degrees of stress-induced diarrhea. Based on these findings, inhibition of 5-HT synthesis relieved the stress response and improved the health of the intestinal tract, including both the intestinal absorption capacity, as determined by the villus height and crypt depth, and the mucosal barrier function, as determined by the tight junction proteins of epithelial cell.

  6. Rapid reversal of human intestinal ischemia-reperfusion induced damage by shedding of injured enterocytes and reepithelialisation.

    Directory of Open Access Journals (Sweden)

    Joep P M Derikx

    . At the same time, M30 immunoreactivity was absent in intact epithelial lining. CONCLUSIONS: This is the first human study to clarify intestinal IR induced cell damage and repair and its direct consequences. It reveals a unique, endogenous clearing mechanism for injured enterocytes: rapid detachment of damaged apoptotic enterocytes into the lumen. This process is followed by repair of the epithelial continuity within an hour, resulting in a normal epithelial lining.

  7. Intestinal Insulin Signaling Encodes Two Different Molecular Mechanisms for the Shortened Longevity Induced by Graphene Oxide in Caenorhabditis elegans

    Science.gov (United States)

    Zhao, Yunli; Yang, Ruilong; Rui, Qi; Wang, Dayong

    2016-04-01

    Graphene oxide (GO) has been shown to cause multiple toxicities in various organisms. However, the underlying molecular mechanisms for GO-induced shortened longevity are still unclear. We employed Caenorhabditis elegans to investigate the possible involvement of insulin signaling pathway in the control of GO toxicity and its underlying molecular mechanisms. Mutation of daf-2, age-1, akt-1, or akt-2 gene induced a resistant property of nematodes to GO toxicity, while mutation of daf-16 gene led to a susceptible property of nematodes to GO toxicity, suggesting that GO may dysregulate the functions of DAF-2/IGF-1 receptor, AGE-1, AKT-1 and AKT-2-mediated kinase cascade, and DAF-16/FOXO transcription factor. Genetic interaction analysis suggested the involvement of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the control of GO toxicity on longevity. Moreover, intestinal RNA interference (RNAi) analysis demonstrated that GO reduced longevity by affecting the functions of signaling cascade of DAF-2-AGE-1-AKT-1/2-DAF-16 in the intestine. DAF-16 could also regulate GO toxicity on longevity by functioning upstream of SOD-3, which encodes an antioxidation system that prevents the accumulation of oxidative stress. Therefore, intestinal insulin signaling may encode two different molecular mechanisms responsible for the GO toxicity in inducing the shortened longevity. Our results highlight the key role of insulin signaling pathway in the control of GO toxicity in organisms.

  8. Deoxynivanelol and Fumonisin, Alone or in Combination, Induce Changes on Intestinal Junction Complexes and in E-Cadherin Expression

    Directory of Open Access Journals (Sweden)

    Karina Basso

    2013-11-01

    Full Text Available Fusariotoxins such as fumonisin B1 (FB1 and deoxynivalenol (DON cause deleterious effects on the intestine of pigs. The aim of this study was to evaluate the effect of these mycotoxins, alone and in combination, on jejunal explants from piglets, using histological, immunohistochemical and ultrastructural assays. Five 24-day old pigs were used for sampling the explants. Forty-eight explants were sampled from each animal. Explants were incubated for 4 hours in culture medium and medium containing FB1 (100 µM, DON (10 µM and both mycotoxins (100 µM FB1 plus 10 µM DON. Exposure to all treatments induced a significant decrease in the normal intestinal morphology and in the number of goblet cells, which were more severe in explants exposed to DON and both mycotoxins. A significant reduction in villus height occurred in groups treated with DON and with co-contamination. Expression of E-cadherin was significantly reduced in explants exposed to FB1 (40%, DON (93% and FB1 plus DON (100%. The ultrastructural assay showed increased intercellular spaces and no junction complexes on enterocytes exposed to mycotoxins. The present data indicate that FB1 and DON induce changes in cell junction complexes that could contribute to increase paracellular permeability. The ex vivo model was adequate for assessing intestinal toxicity induced by exposure of isolated or associated concentrations of 100 µM of FB1 and 10 µM of DON.

  9. Tumor-induced Osteomalacia in a 3-Year-Old With Unresectable Central Giant Cell Lesions.

    Science.gov (United States)

    Crossen, Stephanie S; Zambrano, Eduardo; Newman, Beverley; Bernstein, Jonathan A; Messner, Anna H; Bachrach, Laura K; Twist, Clare J

    2017-01-01

    Tumor-induced osteomalacia (TIO) is a rare cause of hypophosphatemia involving overproduction of fibroblast growth factor 23. TIO has been described largely in adults with small mesenchymal tumors. We report a case of TIO in a child who presented with knee pain and radiographic findings concerning for rickets, and was found to have maxillomandibular giant cell lesions. The patient was treated with oral phosphorus and calcitriol, surgical debulking, and intralesional corticosteroids, which resulted in tumor regression and normalization of serum fibroblast growth factor 23 and phosphorus. This case illustrates the occurrence of this rare paraneoplastic syndrome in children and adds to our knowledge about clinical manifestations and pathologic findings associated with pediatric TIO.

  10. Features of blood serum protein spectrum and cytokine spectrum of rats with chronic carrageenan-induced intestinal inflammation

    Directory of Open Access Journals (Sweden)

    A. S. Tkachenko

    2014-04-01

    Full Text Available It has been established that features of modern diet might be considered as a possible source of inflammatory diseases of gastrointestinal tract. Particular attention is paid to the role of different food additives in the development of intestinal inflammation, including the food additive E407, known as carrageenan. A model of chronic carrageenan-induced gastroenterocolitis of moderate severity has been elaborated, which allows us to study carrageenan-induced intestinal inflammation. In particular, the features of blood serum protein spectrum and cytokine spectrum in chronic carrageenan-induced intestinal inflammation are not studied. The female Wistar rats have been used for the experiment. Chronic carrageenan-induced gastroenterocolitis has been reproduced by the free access of animals to 1% solution of carrageenan in drinking water. Laboratory animals have been divided into 3 groups. Group № 1 consisted of experimental animals, who consumed food additive carrageenan during 2 weeks and group № 2 included experimental animals, who consumed food additive carrageenan during 4 weeks. Group № 3 consisted of intact healthy animals. The development of gastroenterocolitis has been proved morphologically and biochemically. Manipulations with animals have been carried out in accordance with the provisions of the European Convention for the Protection of Vertebrate Animals used for Experimental and other Scientific Purposes (Strasbourg, 1986. It has been established that the disease has been associated with dysproteinemia. The level of α1-globulins increased after 2 weeks of carrageenan consumption and has been normalized in animals, who consumed carrageenan during 4 weeks. The similar changes have been observed for α2-globulins level. It could be explained by production of acute phase proteins, such as α1-acid glycoprotein, C-reactive protein, fibrinogen, α2-macroglobulin, ceruloplasmin, etc. The intake of carrageenan also caused

  11. Repair of UVC induced DNA lesions in erythrocytes from Carassius auratus gibelio

    International Nuclear Information System (INIS)

    Bagdonas, E.; Zukas, K.

    2004-01-01

    The kinetics of UVC (254 nm) irradiation induced DNA single-strand breaks generated during the excision repair of UV induced DNA damage in erythrocytes from Carassius auratus gibelio were studied using alkaline comet assay. Nucleotide excision repair recognised DNA lesions such as UVC induced cyclobutane pyrimidine dimers and 6-4 pyrimidine-pyrimidone photoproducts and produced DNA single-stranded breaks that were easily detected by comet assay. After irradiation of erythrocytes with 58 j/m 2 UVC dose, there was an increase in comet tail moment (CTM) at 2 hours post-radiation, whereas at 4 hours post-radiation CTM decreased and did not differ significantly from the control level (P=0,127). When erythrocytes were exposed to 173 J/m 2 UVC dose, the excision repair delayed in the beginning (0 hours), reached maximum level at 2 hours post-radiation (CTM-54,8) and showed slightly decreased level at 4 hours post-radiation (CTM=18,5). (author)

  12. Protective effect of an herbal preparation (HemoHIM) on radiation-induced intestinal injury in mice.

    Science.gov (United States)

    Kim, Sung Ho; Lee, Hae June; Kim, Joong Sun; Moon, Changjong; Kim, Jong Choon; Park, Hae-Ran; Jung, Uhee; Jang, Jong Sik; Jo, Sung Kee

    2009-12-01

    The protective properties of an herbal preparation (HemoHIM) against intestinal damage were examined by evaluating its effects on jejunal crypt survival, morphological changes, and apoptosis in gamma-irradiated mice. The mice were whole-body irradiated with 12 Gy for the examination of jejunal crypt survival and any morphological changes and with 2 Gy for the detection of apoptosis and Ki-67 labeling. Irradiation was conducted using (60)Co gamma-rays. HemoHIM treatment was administered intraperitonially at a dosage of 50 mg/kg of body weight at 36 and 12 hours pre-irradiation and 30 minutes post-irradiation or orally at a dosage of 250 mg/kg of body weight/day for 7 or 11 days before necropsy. The HemoHIM-treated group displayed a significant increase in survival of jejunal crypts, when compared to the irradiation controls. HemoHIM treatment decreased intestinal morphological changes such as crypt depth, villus height, mucosal length, and basal lamina length of 10 enterocytes after irradiation. Furthermore, the administration of HemoHIM protected intestinal cells from irradiation-induced apoptosis. These results suggested that HemoHIM may be therapeutically useful to reduce intestinal injury following irradiation.

  13. Effects of flavonoids on intestinal inflammation, barrier integrity and changes in gut microbiota during diet-induced obesity.

    Science.gov (United States)

    Gil-Cardoso, Katherine; Ginés, Iris; Pinent, Montserrat; Ardévol, Anna; Blay, Mayte; Terra, Ximena

    2016-12-01

    Diet-induced obesity is associated with low-grade inflammation, which, in most cases, leads to the development of metabolic disorders, primarily insulin resistance and type 2 diabetes. Although prior studies have implicated the adipose tissue as being primarily responsible for obesity-associated inflammation, the latest discoveries have correlated impairments in intestinal immune homeostasis and the mucosal barrier with increased activation of the inflammatory pathways and the development of insulin resistance. Therefore, it is essential to define the mechanisms underlying the obesity-associated gut alterations to develop therapies to prevent and treat obesity and its associated diseases. Flavonoids appear to be promising candidates among the natural preventive treatments that have been identified to date. They have been shown to protect against several diseases, including CVD and various cancers. Furthermore, they have clear anti-inflammatory properties, which have primarily been evaluated in non-intestinal models. At present, a growing body of evidence suggests that flavonoids could exert a protective role against obesity-associated pathologies by modulating inflammatory-related cellular events in the intestine and/or the composition of the microbiota populations. The present paper will review the literature to date that has described the protective effects of flavonoids on intestinal inflammation, barrier integrity and gut microbiota in studies conducted using in vivo and in vitro models.

  14. The Food Contaminants Nivalenol and Deoxynivalenol Induce Inflammation in Intestinal Epithelial Cells by Regulating Reactive Oxygen Species Release

    Directory of Open Access Journals (Sweden)

    Simona Adesso

    2017-12-01

    Full Text Available Fusarium mycotoxins are fungal metabolites whose ability to affect cereal grains as multi-contaminants is progressively increasing. The trichothecene mycotoxins nivalenol (NIV and deoxynivalenol (DON are often found in almost all agricultural commodities worldwide. They are able to affect animal and human health, including at the intestinal level. In this study, NIV, both alone and in combination with DON, induced inflammation and increased the inflammatory response induced by lipopolysaccharide (LPS plus Interferon-γ (IFN in the non-tumorigenic intestinal epithelial cell line (IEC-6. The inflammatory response induced by NIV and DON involves tumor necrosis factor-α (TNF-α production, inducible nitric oxide synthase (iNOS and cyclooxygenase-2 (COX-2 expression, nitrotyrosine formation, reactive oxygen species (ROS release, Nuclear Factor-κB (NF-κB, Nuclear factor (erythroid-derived 2-like 2 (Nrf2 and inflammasome activation. The pro-inflammatory effect was strongly induced by NIV and by the mycotoxin mixture, when compared to DON alone. Mechanistic studies indicate a pivotal role for ROS in the observed pro-inflammatory effects induced by mycotoxins. In this study, the interactions between NIV and DON point out the importance of their food co-contamination, further highlighting the risk assessment process that is of growing concern.

  15. The Food Contaminants Nivalenol and Deoxynivalenol Induce Inflammation in Intestinal Epithelial Cells by Regulating Reactive Oxygen Species Release.

    Science.gov (United States)

    Adesso, Simona; Autore, Giuseppina; Quaroni, Andrea; Popolo, Ada; Severino, Lorella; Marzocco, Stefania

    2017-12-11

    Fusarium mycotoxins are fungal metabolites whose ability to affect cereal grains as multi-contaminants is progressively increasing. The trichothecene mycotoxins nivalenol (NIV) and deoxynivalenol (DON) are often found in almost all agricultural commodities worldwide. They are able to affect animal and human health, including at the intestinal level. In this study, NIV, both alone and in combination with DON, induced inflammation and increased the inflammatory response induced by lipopolysaccharide (LPS) plus Interferon-γ (IFN) in the non-tumorigenic intestinal epithelial cell line (IEC-6). The inflammatory response induced by NIV and DON involves tumor necrosis factor-α (TNF-α) production, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) expression, nitrotyrosine formation, reactive oxygen species (ROS) release, Nuclear Factor-κB (NF-κB), Nuclear factor (erythroid-derived 2)-like 2 (Nrf2) and inflammasome activation. The pro-inflammatory effect was strongly induced by NIV and by the mycotoxin mixture, when compared to DON alone. Mechanistic studies indicate a pivotal role for ROS in the observed pro-inflammatory effects induced by mycotoxins. In this study, the interactions between NIV and DON point out the importance of their food co-contamination, further highlighting the risk assessment process that is of growing concern.

  16. [Secondary male hypogonadism induced by sellar space-occupying lesion: Clinical analysis of 22 cases].

    Science.gov (United States)

    Lu, Hong-Lei; Wang, Tao; Xu, Hao; Chen, Li-Ping; Rao, Ke; Yang, Jun; Yuan, Hui-Xing; Liu, Ji-Hong

    2016-08-01

    To analyze the clinical characteristics of secondary male hypogonadism induced by sellar space-occupying lesion, explore its pathogenesis, and improve its diagnosis and treatment. We retrospectively analyzed the clinical data about 22 cases of secondary male hypogonadism induced by sellar space-occupying lesion, reviewed related literature, and investigated the clinical manifestation, etiological factors, and treatment methods of the disease. Hypogonadism developed in 10 of the patients before surgery and radiotherapy (group A) and in the other 12 after it (group B). The patients received endocrine therapy with Andriol (n=7) or hCG (n=15). The average diameter of the sellar space-occupying lesions was significantly longer in group A than in B ([2.35±0.71] vs [1.83±0.36] cm, P<0.05) and the incidence rate of prolactinomas was markedly higher in the former than in the latter group (60% vs 0, P<0.01). The levels of lutein hormone (LH), follicle stimulating hormone (FSH) and testosterone (T) were remarkably decreased in group B after surgery and radiotherapy (P<0.01). Compared with the parameters obtained before endocrine therapy, all the patients showed significant increases after intervention with Andriol or hCG in the T level ([0.78±0.40] vs [2.71±0.70] ng/ml with Andriol; [0.93±0.44] vs [3.07±0.67] ng/ml with hCG) and IIEF-5 score (5.00±2.61 vs 14.50±3.62 with Andriol; 5.36±1.82 vs 15.07±3.27 with hCG) (all P<0.01). The testis volume increased and pubic hair began to grow in those with hypoevolutism. The patients treated with hCG showed a significantly increased testis volume (P<0.01) and sperm was detected in 7 of them, whose baseline testis volume was markedly larger than those that failed to produce sperm ([11.5±2.3] vs [7.5±2.3] ml, P<0.01). Those treated with Andriol exhibited no significant difference in the testis volume before and after intervention and produced no sperm, either. Hypothyroidism might be attributed

  17. Injury-induced inhibition of small intestinal protein and nucleic acid synthesis

    International Nuclear Information System (INIS)

    Carter, E.A.; Hatz, R.A.; Yarmush, M.L.; Tompkins, R.G.

    1990-01-01

    Small intestinal mucosal weight and nutrient absorption are significantly diminished early after cutaneous thermal injuries. Because these intestinal properties are highly dependent on rates of nucleic acid and protein synthesis, in vivo incorporation of thymidine, uridine, and leucine into small intestinal deoxyribonucleic acid, ribonucleic acid, and proteins were measured. Deoxyribonucleic acid synthesis was markedly decreased with the lowest thymidine incorporation in the jejunum (p less than 0.01); these findings were confirmed by autoradiographic identification of radiolabeled nuclei in the intestinal crypts. Protein synthesis was decreased by 6 h postinjury (p less than 0.01) but had returned to normal by 48 h. Consistent with a decreased rate of protein synthesis, ribonucleic acid synthesis was also decreased 18 h postinjury (p less than 0.01). These decreased deoxyribonucleic acid, ribonucleic acid, and protein synthesis rates are not likely a result of ischemia because in other studies of this injury model, intestinal blood flow was not significantly changed by the burn injury. Potentially, factors initiating the acute inflammatory reaction may directly inhibit nucleic acid and protein synthesis and lead to alterations in nutrient absorption and intestinal barrier function after injury

  18. Lipoteichoic Acid of Probiotic Lactobacillus plantarum Attenuates Poly I:C-Induced IL-8 Production in Porcine Intestinal Epithelial Cells

    Directory of Open Access Journals (Sweden)

    Kyoung Whun Kim

    2017-09-01

    Full Text Available Probiotics in livestock feed supplements are considered a replacement for antibiotics that enhance gastrointestinal immunity. Although bacterial cell wall components have been proposed to be associated with probiotic function, little evidence demonstrates that they are responsible for probiotic functions in livestock. The present study demonstrated that lipoteichoic acid (LTA of Lactobacillus plantarum (Lp.LTA confers anti-inflammatory responses in porcine intestinal epithelial cell line, IPEC-J2. A synthetic analog of viral double-stranded RNA, poly I:C, dose-dependently induced IL-8 production at the mRNA and protein levels in IPEC-J2 cells. Lp.LTA, but not lipoprotein or peptidoglycan from L. plantarum, exclusively suppressed poly I:C-induced IL-8 production. Compared with LTAs from other probiotic Lactobacillus strains including L. delbrueckii, L. sakei, and L. rhamnosus GG, Lp.LTA had higher potential to suppress poly I:C-induced IL-8 production. Dealanylated or deacylated Lp.LTA did not suppress poly I:C-induced IL-8 production, suggesting that D-alanine and lipid moieties in the Lp.LTA structure were responsible for the inhibition. Furthermore, Lp.LTA attenuated the phosphorylation of ERK and p38 kinase as well as the activation of NF-κB, resulting in decreased IL-8 production. Taken together, these results suggest that Lp.LTA acts as an effector molecule to inhibit viral pathogen-induced inflammatory responses in porcine intestinal epithelial cells.

  19. Protective Effect of Repeatedly Preadministered Brazilian Propolis Ethanol Extract against Stress-Induced Gastric Mucosal Lesions in Rats

    Directory of Open Access Journals (Sweden)

    Tadashi Nakamura

    2014-01-01

    Full Text Available The present study was conducted to clarify the protective effect of Brazilian propolis ethanol extract (BPEE against stress-induced gastric mucosal lesions in rats. The protective effect of BPEE against gastric mucosal lesions in male Wistar rats exposed to water-immersion restraint stress (WIRS for 6 h was compared between its repeated preadministration (50 mg/kg/day, 7 days and its single preadministration (50 mg/kg. The repeated BPEE preadministration attenuated WIRS-induced gastric mucosal lesions and gastric mucosal oxidative stress more largely than the single BPEE preadministration. In addition, the repeated BPEE preadministration attenuated neutrophil infiltration in the gastric mucosa of rats exposed to WIRS. The protective effect of the repeated preadministration of BPEE against WIRS-induced gastric mucosal lesions was similar to that of a single preadministration of vitamin E (250 mg/kg in terms of the extent and manner of protection. From these findings, it is concluded that BPEE preadministered in a repeated manner protects against gastric mucosal lesions in rats exposed to WIRS more effectively than BPEE preadministered in a single manner possibly through its antioxidant and anti-inflammatory actions.

  20. Comparsion of light dose on topical ALA-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premalignant lesions

    Science.gov (United States)

    Yang, Deng-Fu; Tseng, Meng-Ke; Liu, Chung-Ji; Hsu, Yih-Chih

    2012-03-01

    Oral cancer has becomes the most prominent male cancer disease due to the local betel nut chewing habit combing with smoking and alcohol-drinking lifestyle. In order to minimize the systemic phototoxic effect of 5-aminolevulinic acid (ALA), this study was designed to use a topical ALA-mediated PDT for treatment of DMBA-induced hamster buccal pouch cancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions were induced and proven by histological examination. These DMBA-induced cancerous lesions were used for testing the efficacy of topical ALA -mediated PDT. We found that ALA reached its peak level in cancerous lesions about 2.5 hrs after topical application of ALA gel. The precancerous lesions in hamsters were then treated with topical ALA -mediated PDT with light exposure dose of 75 and 100 J/cm2 using LED 635 nm Wonderlight device. It is suggesting that optimization of the given light dose is critical to the success of PDT results.

  1. Association of matrix metalloproteinase inducer (EMMPRIN) with the expression of matrix metalloproteinases-1, -2 and -9 during periapical lesion development.

    Science.gov (United States)

    Sousa, Natália Guimarães Kalatzis; Cardoso, Cristina Ribeiro de Barros; Silva, João Satana da; Kuga, Milton Carlos; Tanomaru-Filho, Mário; Faria, Gisele

    2014-09-01

    To evaluate the expression of matrix metalloproteinase inducer (EMMPRIN) and its correlation with the expression of matrix metalloproteinases (MMPs)-1, -2 and -9 during the development of periapical lesion in mice. Periapical lesions were induced in the lower first molars of mice and after 7, 14, 21 and 42 days the mandibles were removed. The periapical lesions were measured by micro-computed tomography. The expression of EMMPRIN, MMPs-1, -2, and -9 genes were determined by real-time RT-PCR. The location and expression of EMMPRIN and MMPs were evaluated by immunohistochemistry. At 14 days, the periapical lesion area was higher than at 7 days. At 21 and 42 days no statistically significant bone loss was observed in comparison to 14 days. The control group showed discrete and occasional EMMPRIM, MMP-1, -2 and -9 immunostaining in the periodontal ligament fibroblasts. At 7, 14, 21 and 42 days intense immunoexpression was observed for EMMPRIN, MMPs-1, -2 and -9 in the region adjacent to the apical foramen. The EMMPRIN immunoexpression was higher at 7, 14, 21 and 42 days compared with the control. There was a positive correlation between gene expression of EMMPRIN and MMPs in the active phase of periapical lesion development. There is a high expression of EMMPRIM mainly by the inflammatory infiltrate in the region adjacent to the apical foramen during periapical lesion development. Furthermore, the positive correlation with MMP-1, -2, and -9 during the first days after periapical lesion induction indicates that EMMPRIM may be involved in the active phase of periapical lesions development. Copyright © 2014 Elsevier Ltd. All rights reserved.

  2. Functional Deficits Precede Structural Lesions in Mice With High-Fat Diet-Induced Diabetic Retinopathy.

    Science.gov (United States)

    Rajagopal, Rithwick; Bligard, Gregory W; Zhang, Sheng; Yin, Li; Lukasiewicz, Peter; Semenkovich, Clay F

    2016-04-01

    Obesity predisposes to human type 2 diabetes, the most common cause of diabetic retinopathy. To determine if high-fat diet-induced diabetes in mice can model retinal disease, we weaned mice to chow or a high-fat diet and tested the hypothesis that diet-induced metabolic disease promotes retinopathy. Compared with controls, mice fed a diet providing 42% of energy as fat developed obesity-related glucose intolerance by 6 months. There was no evidence of microvascular disease until 12 months, when trypsin digests and dye leakage assays showed high fat-fed mice had greater atrophic capillaries, pericyte ghosts, and permeability than controls. However, electroretinographic dysfunction began at 6 months in high fat-fed mice, manifested by increased latencies and reduced amplitudes of oscillatory potentials compared with controls. These electroretinographic abnormalities were correlated with glucose intolerance. Unexpectedly, retinas from high fat-fed mice manifested striking induction of stress kinase and neural inflammasome activation at 3 months, before the development of systemic glucose intolerance, electroretinographic defects, or microvascular disease. These results suggest that retinal disease in the diabetic milieu may progress through inflammatory and neuroretinal stages long before the development of vascular lesions representing the classic hallmark of diabetic retinopathy, establishing a model for assessing novel interventions to treat eye disease. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  3. Oral Lesions Induced by Chronic Khat Use Consist Essentially of Thickened Hyperkeratinized Epithelium

    Directory of Open Access Journals (Sweden)

    Ochiba Mohammed Lukandu

    2015-01-01

    Full Text Available Objectives. The habit of khat chewing is prevalent in many Middle Eastern and African cultures and has been associated with various adverse conditions in humans. This study aimed to describe histological changes induced by chronic khat chewing on the buccal mucosa. Methods. Biopsies of the buccal mucosa from 14 chronic khat chewers, 20 chronic khat chewers who also smoked tobacco, and 8 nonchewers were compared for epithelial thickness, degree and type of keratinization, and connective tissue changes. Results. Tissues from khat chewers depicted abnormal keratinization of the superficial cell layer and showed increased epithelial thickness affecting all layers. Epithelial thickness in control samples was 205 ± 26 μm whereas thickness in khat chewers and khat chewers who smoked tobacco was significantly higher measuring 330 ± 35 μm and 335 ± 19 μm, respectively. Tissues from khat chewers also showed increased intracellular edema, increased melanin pigment deposits, and increased number of rete pegs most of which were thin and deep. Conclusions. These results show that oral lesions induced by chronic chewing of khat in the buccal mucosa present with white and brown discoloration due to increased epithelial thickness, increased keratinization, and melanin deposition.

  4. Intestinal flora imbalance promotes alcohol-induced liver fibrosis by the TGFβ/smad signaling pathway in mice.

    Science.gov (United States)

    Zhang, Dong; Hao, Xiuxian; Xu, Lili; Cui, Jing; Xue, Li; Tian, Zibin

    2017-10-01

    Intestinal flora performs a crucial role in human health and its imbalance may cause numerous pathological changes. The liver can also affect the intestinal function through bile secretion via the enterohepatic cycle. The pathophysiological association between the gut and the liver is described as the gut-liver axis. The present study investigated the role of intestinal flora in alcohol-induced liver fibrosis. A total of 36 C57 mice were randomly and equally divided into 3 different dietary regimes: Group I (alcohol injury; received alcohol); group II (alcohol injury with flora imbalance; received alcohol plus lincomycin hydrochloride) and group III (alcohol injury with corrected flora imbalance; received alcohol, lincomycin hydrochloride and extra probiotics). The present study then investigated several indicators of liver damage. Alkaline phosphatase (ALP) levels, aspartate aminotransferase (AST) levels and alanine aminotransferase (ALT) levels in mice serum were studied. Masson staining and Annexin V-fluorescein isothiocyanate/propidium iodide double staining was also performed, and the expression of mothers against decapentaplegic homolog (smad) 3 and smad4 proteins in hepatic stellate cells (HSCs) of the mice was examined using western blot analysis. The levels of serum ALP, AST and ALT were the highest in group II mice, and all 3 levels decreased in group III mice compared with those from group II. The degree of liver fibrosis was aggravated in group II mice compared with group I mice. The apoptosis of HSCs was significantly inhibited in group II mice, but was increased in group III mice. The HSCs in group II mice exhibited higher expression of smad3 and smad4, whilst group III mice (with corrected intestinal flora imbalance) exhibited downregulated expression of smad3 and smad4. The present data indicates that the intestinal flora perform a significant role in maintaining liver homeostasis. Furthermore, an imbalance of intestinal flora can exacerbate alcohol-induced

  5. Vestibular lesion-induced developmental plasticity in spinal locomotor networks during Xenopus laevis metamorphosis.

    Science.gov (United States)

    Beyeler, Anna; Rao, Guillaume; Ladepeche, Laurent; Jacques, André; Simmers, John; Le Ray, Didier

    2013-01-01

    During frog metamorphosis, the vestibular sensory system remains unchanged, while spinal motor networks undergo a massive restructuring associated with the transition from the larval to adult biomechanical system. We investigated in Xenopus laevis the impact of a pre- (tadpole stage) or post-metamorphosis (juvenile stage) unilateral labyrinthectomy (UL) on young adult swimming performance and underlying spinal locomotor circuitry. The acute disruptive effects on locomotion were similar in both tadpoles and juvenile frogs. However, animals that had metamorphosed with a preceding UL expressed restored swimming behavior at the juvenile stage, whereas animals lesioned after metamorphosis never recovered. Whilst kinematic and electrophysiological analyses of the propulsive system showed no significant differences in either juvenile group, a 3D biomechanical simulation suggested that an asymmetry in the dynamic control of posture during swimming could account for the behavioral restoration observed in animals that had been labyrinthectomized before metamorphosis. This hypothesis was subsequently supported by in vivo electromyography during free swimming and in vitro recordings from isolated brainstem/spinal cord preparations. Specifically, animals lesioned prior to metamorphosis at the larval stage exhibited an asymmetrical propulsion/posture coupling as a post-metamorphic young adult. This developmental alteration was accompanied by an ipsilesional decrease in propriospinal coordination that is normally established in strict left-right symmetry during metamorphosis in order to synchronize dorsal trunk muscle contractions with bilateral hindlimb extensions in the swimming adult. Our data thus suggest that a disequilibrium in descending vestibulospinal information during Xenopus metamorphosis leads to an altered assembly of adult spinal locomotor circuitry. This in turn enables an adaptive compensation for the dynamic postural asymmetry induced by the vestibular imbalance

  6. Impact of whey proteins on the systemic and local intestinal level of mice with diet induced obesity.

    Science.gov (United States)

    Swiątecka, D; Złotkowska, D; Markiewicz, L H; Szyc, A M; Wróblewska, B

    2017-04-19

    Obesity is a serious public health problem and being multifactorial is difficult to tackle. Since the intestinal ecosystem's homeostasis is, at least partially, diet-dependent, its modulation may be triggered by food components that are designed to exert a modulatory action leading to a health-promoting effect. Milk whey proteins, are considered as such promising factors since they influence satiation as well as body weight and constitute the source of biologically active peptides which may modulate health status locally and systemically. This way, whey proteins are associated with obesity. Therefore, this paper is aimed at the estimation of the impact of whey proteins using a commercially available whey protein isolate on the physiological response of mice with diet-induced obesity. The physiological response was evaluated on the local-intestinal level, scrutinizing intestinal microbiota as one of the important factors in obesity and on the systemic level, analyzing the response of the organism. Whey proteins brought about the decrease of the fat mass with a simultaneous increase of the lean mass of animals with diet induced obesity, which is a promising, health-promoting effect. Whey proteins also proved to act beneficially helping restore the number of beneficial bifidobacteria in obese animals and decreasing the calorie intake and fat mass as well as the LDL level. Overall, supplementation of the high fat diet with whey proteins acted locally by restoration of the intestinal ecosystem, thus preventing dysbiosis and its effects and also acted systemically by strengthening the organism increasing the lean mass and thus hindering obesity-related detrimental effects.

  7. Improvement of cerebral hypometabolism after resection of radiation-induced necrotic lesion in a patient with cerebral arteriovenous malformation

    International Nuclear Information System (INIS)

    Harada, Yae; Hirata, Kenji; Nakayama, Naoki; Yamaguchi, Shigeru; Yoshida, Michiharu; Onodera, Shunsuke; Manabe, Osamu; Shiga, Tohru; Terae, Satoshi; Shirato, Hiroki; Tamaki, Nagara

    2015-01-01

    A 55-year-old woman underwent radiosurgery for a left cerebral hemisphere arteriovenous malformation (AVM) and developed radiation-induced necrosis causing a massive edema in the surrounding brain tissues. Despite various therapies, the edema expanded to the ipsilateral hemisphere and induced neurological symptoms. The radiation-induced necrotic lesion was surgically removed 4 years after radiosurgery. While the preoperative FDG PET revealed severe hypometabolism in the left cerebrum, the necrotomy significantly ameliorated the brain edema, glucose metabolism (postoperative FDG PET), and symptoms. This case indicates that radiation necrosis-induced neurological deficits may be associated with brain edema and hypometabolism, which could be reversed by appropriate necrotomy

  8. Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

    International Nuclear Information System (INIS)

    Cianfoni, A.; Caulo, M.; Cerase, A.; Della Marca, G.; Falcone, C.; Di Lella, G.M.; Gaudino, S.; Edwards, J.; Colosimo, C.

    2013-01-01

    Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention

  9. Seizure-induced brain lesions: A wide spectrum of variably reversible MRI abnormalities

    Energy Technology Data Exchange (ETDEWEB)

    Cianfoni, A., E-mail: acianfoni@hotmail.com [Neuroradiology, Neurocenter of Italian Switzerland–Ospedale regionale Lugano, Via Tesserete 46, Lugano, 6900, CH (Switzerland); Caulo, M., E-mail: caulo@unich.it [Department of Neuroscience and Imaging, University of Chieti, Via dei Vestini 33, 6610 Chieti. Italy (Italy); Cerase, A., E-mail: alfonsocerase@gmail.com [Unit of Neuroimaging and Neurointervention NINT, Department of Neurological and Sensorineural Sciences, Azienda Ospedaliera Universitaria Senese, Policlinico “Santa Maria alle Scotte”, V.le Bracci 16, Siena (Italy); Della Marca, G., E-mail: dellamarca@rm.unicatt.it [Neurology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Falcone, C., E-mail: carlo_falc@libero.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Di Lella, G.M., E-mail: gdilella@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Gaudino, S., E-mail: sgaudino@sirm.org [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy); Edwards, J., E-mail: edwardjc@musc.edu [Neuroscience Dept., Medical University of South Carolina, 96J Lucas st, 29425, Charleston, SC (United States); Colosimo, C., E-mail: colosimo@rm.unicatt.it [Radiology Dept., Catholic University of Rome, L.go F Vito 1, 00100, Rome (Italy)

    2013-11-01

    Introduction MRI abnormalities in the postictal period might represent the effect of the seizure activity, rather than its structural cause. Material and Methods Retrospective review of clinical and neuroimaging charts of 26 patients diagnosed with seizure-related MR-signal changes. All patients underwent brain-MRI (1.5-Tesla, standard pre- and post-contrast brain imaging, including DWI-ADC in 19/26) within 7 days from a seizure and at least one follow-up MRI, showing partial or complete reversibility of the MR-signal changes. Extensive clinical work-up and follow-up, ranging from 3 months to 5 years, ruled out infection or other possible causes of brain damage. Seizure-induced brain-MRI abnormalities remained a diagnosis of exclusion. Site, characteristics and reversibility of MRI changes, and association with characteristics of seizures were determined. Results MRI showed unilateral (13/26) and bilateral abnormalities, with high (24/26) and low (2/26) T2-signal, leptomeningeal contrast-enhancement (2/26), restricted diffusion (9/19). Location of abnormality was cortical/subcortical, basal ganglia, white matter, corpus callosum, cerebellum. Hippocampus was involved in 10/26 patients. Reversibility of MRI changes was complete in 15, and with residual gliosis or focal atrophy in 11 patients. Reversibility was noted between 15 and 150 days (average, 62 days). Partial simple and complex seizures were associated with hippocampal involvement (p = 0.015), status epilepticus with incomplete reversibility of MRI abnormalities (p = 0.041). Conclusions Seizure or epileptic status can induce transient, variably reversible MRI brain abnormalities. Partial seizures are frequently associated with hippocampal involvement and status epilepticus with incompletely reversible lesions. These seizure-induced MRI abnormalities pose a broad differential diagnosis; increased awareness may reduce the risk of misdiagnosis and unnecessary intervention.

  10. The role of thymus-dependent T cells in hexachlorobenzene-induced inflammatory skin and lung lesions

    NARCIS (Netherlands)

    Michielsen, CCPPC; Bloksma, N; Klatter, FA; Rozing, J; Vos, JG; van Dijk, JE

    1999-01-01

    The involvement of thymus-dependent T cells in the inflammatory skin and lung lesions and spleen effects induced by hexachlorobenzene (HCB) was investigated by using genetically athymic and euthymic WAG/Rij rats and Brown Norway (BN) rats with or without depletion of T cells by adult thymectomy,

  11. Butyrate attenuates lipopolysaccharide-induced inflammation in intestinal cells and Crohn's mucosa through modulation of antioxidant defense machinery.

    Directory of Open Access Journals (Sweden)

    Ilaria Russo

    Full Text Available Oxidative stress plays an important role in the pathogenesis of inflammatory bowel disease (IBD, including Crohn's disease (CrD. High levels of Reactive Oxygen Species (ROS induce the activation of the redox-sensitive nuclear transcription factor kappa-B (NF-κB, which in turn triggers the inflammatory mediators. Butyrate decreases pro-inflammatory cytokine expression by the lamina propria mononuclear cells in CrD patients via inhibition of NF-κB activation, but how it reduces inflammation is still unclear. We suggest that butyrate controls ROS mediated NF-κB activation and thus mucosal inflammation in intestinal epithelial cells and in CrD colonic mucosa by triggering intracellular antioxidant defense systems. Intestinal epithelial Caco-2 cells and colonic mucosa from 14 patients with CrD and 12 controls were challenged with or without lipopolysaccaride from Escherichia coli (EC-LPS in presence or absence of butyrate for 4 and 24 h. The effects of butyrate on oxidative stress, p42/44 MAP kinase phosphorylation, p65-NF-κB activation and mucosal inflammation were investigated by real time PCR, western blot and confocal microscopy. Our results suggest that EC-LPS challenge induces a decrease in Gluthation-S-Transferase-alpha (GSTA1/A2 mRNA levels, protein expression and catalytic activity; enhanced levels of ROS induced by EC-LPS challenge mediates p65-NF-κB activation and inflammatory response in Caco-2 cells and in CrD colonic mucosa. Furthermore butyrate treatment was seen to restore GSTA1/A2 mRNA levels, protein expression and catalytic activity and to control NF-κB activation, COX-2, ICAM-1 and the release of pro-inflammatory cytokine. In conclusion, butyrate rescues the redox machinery and controls the intracellular ROS balance thus switching off EC-LPS induced inflammatory response in intestinal epithelial cells and in CrD colonic mucosa.

  12. Symbiotic formulation in experimentally induced liver fibrosis in rats: intestinal microbiota as a key point to treat liver damage?

    Science.gov (United States)

    D'Argenio, Giuseppe; Cariello, Rita; Tuccillo, Concetta; Mazzone, Giovanna; Federico, Alessandro; Funaro, Annalisa; De Magistris, Laura; Grossi, Enzo; Callegari, Maria L; Chirico, Marilena; Caporaso, Nicola; Romano, Marco; Morelli, Lorenzo; Loguercio, Carmela

    2013-05-01

    Evidence indicates that intestinal microbiota may participate in both the induction and the progression of liver damage. The aim of our research was the detection and evaluation of the effects of chronic treatment with a symbiotic formulation on CCl4 -induced rat liver fibrosis. CCl4 significantly increased gastric permeability in respect to basal values, and the treatment with symbiotic significantly decreased it. CCl4 per se induced a decrease in intestinal permeability. This effect was also seen in fibrotic rats treated with symbiotic and was still evident when normal rats were treated with symbiotic alone (P symbiotic treatment normalized the plasma levels of TNF-α and significantly enhanced anti-inflammatory cytokine IL 10. TNF-α, TGF-β, TLR4, TLR2, iNOS and α-SMA mRNA expression in the liver were up-regulated in rats with CCl4 -induced liver fibrosis and down-regulated by symbiotic treatment. Moreover, IL-10 and eNOS mRNA levels were increased in the CCL4 (+) symbiotic group. Symbiotic treatment of fibrotic rats normalized serum ALT, AST and improved histology and liver collagen deposition. DGGE analysis of faecal samples revealed that CCl4 administration and symbiotic treatment either alone or in combination produced modifications in faecal profiles vs controls. Our results provide evidence that in CCl4 -induced liver fibrosis, significant changes in gastro-intestinal permeability and in faecal flora occur. Treatment with a specific symbiotic formulation significantly affects these changes, leading to improvement in both liver inflammation and fibrosis. © 2013 John Wiley & Sons A/S.

  13. Mitochondrial dysfunction is responsible for the intestinal calcium absorption inhibition induced by menadione.

    Science.gov (United States)

    Marchionatti, Ana M; Perez, Adriana V; Diaz de Barboza, Gabriela E; Pereira, Beatriz M; Tolosa de Talamoni, Nori G

    2008-02-01

    Menadione (MEN) inhibits intestinal calcium absorption by a mechanism not completely understood. The aim of this work was to find out the role of mitochondria in this inhibitory mechanism. Hence, normal chicks treated with one i.p. dose of MEN were studied in comparison with controls. Intestinal calcium absorption was measured by the in situ ligated intestinal segment technique. GSH, oxidoreductase activities from the Krebs cycle and enzymes of the antioxidant system were measured in isolated mitochondria. Mitochondrial membrane potential was measured by a flow cytometer technique. DNA fragmentation and cytochrome c localization were determined by immunocytochemistry. Data indicate that in 30 min, MEN decreases intestinal Ca(2+) absorption, which returns to the control values after 10 h. GSH was only decreased for half an hour, while the activity of malate dehydrogenase and alpha-ketoglutarate dehydrogenase was diminished for 48 h. Mn(2+)-superoxide dismutase activity was increased in 30 min, whereas the activity of catalase and glutathione peroxidase remained unaltered. DNA fragmentation and cytochrome c release were maximal in 30 min, but were recovered after 15 h. In conclusion, MEN inhibits intestinal Ca(2+) absorption by mitochondrial dysfunction as revealed by GSH depletion and alteration of the permeability triggering the release of cytochrome c and DNA fragmentation.

  14. Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity.

    Science.gov (United States)

    Zhong, Ze-Yu; Sun, Bin-Bin; Shu, Nan; Xie, Qiu-Shi; Tang, Xian-Ge; Ling, Zhao-Li; Wang, Fan; Zhao, Kai-Jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-Zhu; Liu, Xiao-Dong

    2016-07-01

    Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestinediclofenac, typical enteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via the inhibition of intestinal β-glucuronidase activity.

  15. Ciprofloxacin blocked enterohepatic circulation of diclofenac and alleviated NSAID-induced enteropathy in rats partly by inhibiting intestinal β-glucuronidase activity

    Science.gov (United States)

    Zhong, Ze-yu; Sun, Bin-bin; Shu, Nan; Xie, Qiu-shi; Tang, Xian-ge; Ling, Zhao-li; Wang, Fan; Zhao, Kai-jing; Xu, Ping; Zhang, Mian; Li, Ying; Chen, Yang; Liu, Li; Xia, Lun-zhu; Liu, Xiao-dong

    2016-01-01

    Aim: Diclofenac is a non-steroidal anti-inflammatory drug (NSAID), which may cause serious intestinal adverse reactions (enteropathy). In this study we investigated whether co-administration of ciprofloxacin affected the pharmacokinetics of diclofenac and diclofenac-induced enteropathy in rats. Methods: The pharmacokinetics of diclofenac was assessed in rats after receiving diclofenac (10 mg/kg, ig, or 5 mg/kg, iv), with or without ciprofloxacin (20 mg/kg, ig) co-administered. After receiving 6 oral doses or 15 intravenous doses of diclofenac, the rats were sacrificed, and small intestine was removed to examine diclofenac-induced enteropathy. β-Glucuronidase activity in intestinal content, bovine liver and E coli was evaluated. Results: Following oral or intravenous administration, the pharmacokinetic profile of diclofenac displayed typical enterohepatic circulation, and co-administration of ciprofloxacin abolished the enterohepatic circulation, resulted in significant reduction in the plasma content of diclofenac. In control rats, β-glucuronidase activity in small intestinal content was region-dependent: proximal intestinediclofenac, typical enteropathy was developed with severe enteropathy occurred in distal small intestine. Co-administration of ciprofloxacin significantly alleviated diclofenac-induced enteropathy. Conclusion: Co-administration of ciprofloxacin attenuated enterohepatic circulation of diclofenac and alleviated diclofenac-induced enteropathy in rats, partly via the inhibition of intestinal β-glucuronidase activity. PMID:27180979

  16. Systemic sclerosis complicated with localized scleroderma-like lesions induced by Köbner phenomenon.

    Science.gov (United States)

    Saigusa, Ryosuke; Asano, Yoshihide; Yamashita, Takashi; Takahashi, Takehiro; Nakamura, Kouki; Miura, Shunsuke; Ichimura, Yohei; Toyama, Tetsuo; Taniguchi, Takashi; Sumida, Hayakazu; Tamaki, Zenshiro; Miyazaki, Miki; Yoshizaki, Ayumi; Sato, Shinichi

    2018-03-01

    Scleroderma is a chronic disease of unknown etiology characterized by skin fibrosis and is divided into two clinical entities: systemic sclerosis (SSc) and localized scleroderma (LSc). In general, LSc is rarely complicated with SSc, but a certain portion of SSc patients manifests bilateral symmetric LSc-like lesions on the trunk and extremities. We investigated SSc patients with LSc-like lesions to clarify the underlying pathophysiology. Nine SSc cases complicated with LSc-like lesions were clinically and histologically characterized. SSc patients with LSc-like lesions exhibited multiple progressive hyper- and/or hypo-pigmented plaques with mild sclerosis symmetrically distributed on the trunk and extremities, especially abdominal region. In histological assessment, epidermal IL-1α expression was elevated in both forearms and LSc-like lesions of these patients to a greater extent than in forearms of control patients (SSc patients without LSc-like lesions). Of note, the infiltration and degranulation of mast cells were evident throughout the dermis of LSc-like lesions, while detectable to a lesser extent in forearms of SSc patients with LSc-like lesions and control patients. The epidermis of SSc patients with LSc-like lesions seems to possess an inflammatory phenotype, leading to the activation of mast cells in the dermis of mechanically stressed skin. Köbner phenomenon may be involved in the induction of LSc-like lesions in a certain subset of SSc. Copyright © 2017 Japanese Society for Investigative Dermatology. Published by Elsevier B.V. All rights reserved.

  17. Poly(ADP-ribose) polymerase 1 escorts XPC to UV-induced DNA lesions during nucleotide excision repair.

    Science.gov (United States)

    Robu, Mihaela; Shah, Rashmi G; Purohit, Nupur K; Zhou, Pengbo; Naegeli, Hanspeter; Shah, Girish M

    2017-08-15

    Xeroderma pigmentosum C (XPC) protein initiates the global genomic subpathway of nucleotide excision repair (GG-NER) for removal of UV-induced direct photolesions from genomic DNA. The XPC has an inherent capacity to identify and stabilize at the DNA lesion sites, and this function is facilitated in the genomic context by UV-damaged DNA-binding protein 2 (DDB2), which is part of a multiprotein UV-DDB ubiquitin ligase complex. The nuclear enzyme poly(ADP-ribose) polymerase 1 (PARP1) has been shown to facilitate the lesion recognition step of GG-NER via its interaction with DDB2 at the lesion site. Here, we show that PARP1 plays an additional DDB2-independent direct role in recruitment and stabilization of XPC at the UV-induced DNA lesions to promote GG-NER. It forms a stable complex with XPC in the nucleoplasm under steady-state conditions before irradiation and rapidly escorts it to the damaged DNA after UV irradiation in a DDB2-independent manner. The catalytic activity of PARP1 is not required for the initial complex formation with XPC in the nucleoplasm but it enhances the recruitment of XPC to the DNA lesion site after irradiation. Using purified proteins, we also show that the PARP1-XPC complex facilitates the handover of XPC to the UV-lesion site in the presence of the UV-DDB ligase complex. Thus, the lesion search function of XPC in the genomic context is controlled by XPC itself, DDB2, and PARP1. Our results reveal a paradigm that the known interaction of many proteins with PARP1 under steady-state conditions could have functional significance for these proteins.

  18. Hypotonicity induced K+ and anion conductive pathways activation in eel intestinal epithelium

    DEFF Research Database (Denmark)

    Lionetto, M G; Giordano, M E; De Nuccio, F

    2005-01-01

    , the activation of 'emergency' systems of rapid cell volume regulation is fundamental in their physiology. The aim of the present work was to study the physiological response to hypotonic stress in a salt-transporting epithelium, the intestine of the euryhaline teleost Anguilla anguilla. Eel intestinal epithelium......, when symmetrically bathed with Ringer solution, develops a net Cl- current giving rise to a negative transepithelial potential at the basolateral side of the epithelium. The eel intestinal epithelium responded to a hypotonic challenge with a biphasic decrease in the transepithelial voltage (V......(te)) and the short circuit current (I(sc)). This electrophysiological response correlated with a regulatory volume decrease (RVD) response, recorded by morphometrical measurement of the epithelium height. Changes in the transepithelial resistance were also observed following the hypotonicity exposure...

  19. Topical efficacy of dimercapto-chelating agents against lewisite-induced skin lesions in SKH-1 hairless mice

    Energy Technology Data Exchange (ETDEWEB)

    Mouret, Stéphane, E-mail: stephane.mouret@irba.fr [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Wartelle, Julien; Emorine, Sandy; Bertoni, Marine; Nguon, Nina; Cléry-Barraud, Cécile [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Dorandeu, Frédéric [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France); Ecole du Val-de-Grâce, 1 place Alphonse Laveran, Paris (France); Boudry, Isabelle [Département de Toxicologie et Risques Chimiques, Institut de Recherche Biomédicale des Armées, Centre de Recherches du Service de Santé des Armées, 24 avenue Maquis du Grésivaudan, 38700 La Tronche (France)

    2013-10-15

    Lewisite is a potent chemical warfare arsenical vesicant that can cause severe skin lesions. Today, lewisite exposure remains possible during demilitarization of old ammunitions and as a result of deliberate use. Although its cutaneous toxicity is not fully elucidated, a specific antidote exists, the British anti-lewisite (BAL, dimercaprol) but it is not without untoward effects. Analogs of BAL, less toxic, have been developed such as meso-2,3-dimercaptosuccinic acid (DMSA) and have been employed for the treatment of heavy metal poisoning. However, efficacy of DMSA against lewisite-induced skin lesions remains to be determined in comparison with BAL. We have thus evaluated in this study the therapeutic efficacy of BAL and DMSA in two administration modes against skin lesions induced by lewisite vapor on SKH-1 hairless mice. Our data demonstrate a strong protective efficacy of topical application of dimercapto-chelating agents in contrast to a subcutaneous administration 1 h after lewisite exposure, with attenuation of wound size, necrosis and impairment of skin barrier function. The histological evaluation also confirms the efficacy of topical application by showing that treatments were effective in reversing lewisite-induced neutrophil infiltration. This protective effect was associated with an epidermal hyperplasia. However, for all the parameters studied, BAL was more effective than DMSA in reducing lewisite-induced skin injury. Together, these findings support the use of a topical form of dimercaprol-chelating agent against lewisite-induced skin lesion within the first hour after exposure to increase the therapeutic management and that BAL, despite its side-effects, should not be abandoned. - Highlights: • Topically applied dimercapto-chelating agents reduce lewisite-induced skin damage. • One topical application of BAL or DMSA is sufficient to reverse lewisite effects. • Topical BAL is more effective than DMSA to counteract lewisite-induced skin damage.

  20. LPS-induced genes in intestinal tissue of the sea cucumber Holothuria glaberrima.

    Directory of Open Access Journals (Sweden)

    Francisco Ramírez-Gómez

    2009-07-01

    Full Text Available Metazoan immunity is mainly associated with specialized cells that are directly involved with the immune response. Nevertheless, both in vertebrates and invertebrates other organs might respond to immune activation and participate either directly or indirectly in the ongoing immune process. However, most of what is known about invertebrate immunity has been restricted to immune effector cells and little information is available on the immune responses of other tissues or organs. We now focus on the immune reactions of the intestinal tissue of an echinoderm. Our study employs a non-conventional model, the echinoderm Holothuria glaberrima, to identify intestinal molecules expressed after an immune challenge presented by an intra-coelomic injection of lipopolysaccharides (LPS. The expression profiles of intestinal genes expressed differentially between LPS-injected animals and control sea water-injected animals were determined using a custom-made Agilent microarray with 7209 sea cucumber intestinal ESTs. Fifty (50 unique sequences were found to be differentially expressed in the intestine of LPS-treated sea cucumbers. Seven (7 of these sequences represented homologues of known proteins, while the remaining (43 had no significant similarity with any protein, EST or RNA database. The known sequences corresponded to cytoskeletal proteins (Actin and alpha-actinin, metabolic enzymes (GAPDH, Ahcy and Gnmt, metal ion transport/metabolism (major yolk protein and defense/recognition (fibrinogen-like protein. The expression pattern of 11 genes was validated using semi-quantitative RT-PCR. Nine of these corroborated the microarray results and the remaining two showed a similar trend but without statistical significance. Our results show some of the molecular events by which the holothurian intestine responds to an immune challenge and provide important information to the study of the evolution of the immune response.

  1. Saccharomyces boulardii ameliorates clarithromycin- and methotrexate-induced intestinal and hepatic injury in rats.

    Science.gov (United States)

    Duman, Deniz Güney; Kumral, Zarife Nigâr Özdemir; Ercan, Feriha; Deniz, Mustafa; Can, Güray; Cağlayan Yeğen, Berrak

    2013-08-28

    Saccharomyces boulardii is a probiotic used for the prevention of antibiotic-associated diarrhoea. We aimed to investigate whether S. boulardii could alter the effects of clarithromycin (CLA) and methotrexate (MTX) on oro-caecal intestinal transit and oxidative damage in rats. Rats were divided into two groups receiving a single dose of MTX (20 mg/kg) or CLA (20 mg/kg per d) for 1 week. Groups were treated with either saline or S. boulardii (500 mg/kg) twice per d throughout the experiment. The control group was administered only saline. Following decapitation, intestinal transit and inflammation markers of glutathione (GSH), malondialdehyde and myeloperoxidase were measured in intestinal and hepatic tissues. CLA and MTX increased intestinal transit, while S. boulardii treatment slowed down CLA-facilitated transit back to control level. Both MTX and CLA increased lipid peroxidation while depleting the antioxidant GSH content in the hepatic and ileal tissues. Conversely, lipid peroxidation was depressed and GSH levels were increased in the ileal and hepatic tissues of S. boulardii-treated rats. Increased ileal neutrophil infiltration due to MTX and CLA treatments was also reduced by S. boulardii treatment. Histological analysis supported that S. boulardii protected intestinal tissues against the inflammatory effects of both agents. These findings suggest that S. boulardii ameliorates intestinal injury and the accompanying hepatic inflammation by supporting the antioxidant state of the tissues and by inhibiting the recruitment of neutrophils. Moreover, a preventive effect on MTXinduced toxicity is a novel finding of S. boulardii, proposing it as an adjunct to chemotherapy regimens.

  2. Enteral peptide formulas inhibit radiation induced enteritis and apoptosis in intestinal epithelial cells and suppress the expression and function of Alzheimer's and cell division control gene products

    International Nuclear Information System (INIS)

    Cope, F.O.; Issinger, O.G.; McArdle, A.H.; Shapiro, J.; Tomei, L.D.

    1991-01-01

    Studies have shown that patients receiving enteral peptide formulas prior to irradiation have a significantly reduced incidence of enteritis and express a profound increase in intestinal cellularity. Two conceptual approaches were taken to describe this response. First was the evaluation in changes in programmed intestinal cell death and secondly the evaluation of a gene product controlling cell division cycling. This study provided a relationship between the ratio of cell death to cell formulations. The results indicate that in the canine and murine models, irradiation induces expression of the Alzheimer's gene in intestinal crypt cells, while the incidence of apoptosis in apical cells is significantly increased. The use of peptide enteral formulations suppresses the expression of the Alzheimer's gene in crypt cells, while apoptosis is eliminated in the apical cells of the intestine. Concomitantly, enteral peptide formulations suppress the function of the CK-II gene product in the basal and baso-lateral cells of the intestine. These data indicate that although the mitotic index is significantly reduced in enterocytes, this phenomenon alone is not sufficient to account for the peptide-induced radio-resistance of the intestine. The data also indicate a significant reduction of normal apoptosis in the upper lateral and apical cells of the intestinal villi. Thus, the ratio of cell death to cell replacement is significantly decreased resulting in an increase in villus height and hypertrophy of the apical villus cells. Thus, peptide solutions should be considered as an adjunct treatment both in radio- and chemotherapy

  3. Radiation-induced intestinal neoplasia in a genetically-predisposed mouse (Min)

    International Nuclear Information System (INIS)

    Ellender, M.; Larder, S.M.; Harrison, J.D.; Cox, R.; Silver, A.R.J.

    1997-01-01

    A mouse lineage with inherited predisposition to multiple intestinal neoplasia (min) has been proposed as a model to study human colorectal cancer. Min mice are heterozygous for the adenomatous polyposis coli (Apc) gene implicated in human familial adenomatous polyposis (FAP). There is an increased risk of intestinal cancer in humans following radiation exposure and the min mouse model may be used to further our understanding of the molecular mechanisms involved. The present study showed a 2 Gy dose of x-rays doubles the tumour numbers in the murine gastrointestinal tract of F1 min heterozygotes. The distribution of tumours through the gut was also recorded. (authors)

  4. Bax and Bak Do Not Exhibit Functional Redundancy in Mediating Radiation-Induced Endothelial Apoptosis in the Intestinal Mucosa

    International Nuclear Information System (INIS)

    Rotolo, Jimmy A.; Maj, Jerzy G.; Feldman, Regina; Ren, Decheng; Haimovitz-Friedman, Adriana; Cordon-Cardo, Carlos; Cheng, Emily H.-Y.; Kolesnick, Richard; Fuks, Zvi

    2008-01-01

    Purpose: To address in vivo the issue of whether Bax and Bak are functionally redundant in signaling apoptosis, capable of substituting for each other. Methods and Materials: Mice were exposed to whole-body radiation, and endothelial cell apoptosis was quantified using double immunostaining with TUNEL and anti-CD31 antibody. Crypt survival was determined at 3.5 days after whole-body radiation by the microcolony survival assay. Actuarial animal survival was calculated by the product-limit Kaplan-Meier method, and autopsies were performed to establish cause of death. Results: Radiation exposure of Bax- and Bak-deficient mice, both expressing a wild-type acid sphingomyelinase (ASMase) phenotype, indicated that Bax and Bak are both mandatory, though mutually independent, for the intestinal endothelial apoptotic response. However, neither affected epithelial apoptosis at crypt positions 4-5, indicating specificity toward endothelium. Furthermore, Bax deficiency and Bak deficiency each individually mimicked ASMase deficiency in inhibiting crypt lethality in the microcolony assay and in rescuing mice from the lethal gastrointestinal syndrome. Conclusions: The data indicate that Bax and Bak have nonredundant functional roles in the apoptotic response of the irradiated intestinal endothelium. The observation that Bax deficiency and Bak deficiency also protect crypts in the microcolony assay provides strong evidence that the microvascular apoptotic component is germane to the mechanism of radiation-induced damage to mouse intestines, regulating reproductive cell death of crypt stem cell clonogens

  5. Differential effects of unilateral lesions in the medial amygdala on spontaneous and induced ovulation.

    Science.gov (United States)

    Sanchez, M A; Dominguez, R

    1995-01-01

    The possible existence of asymmetry in the control of ovulation by the medial amygdala was explored. Unilateral lesions of the medial amygdala were performed on each day of the estrous cycle. The estral index diminished in almost all animals with a lesion in the right side of medial amygdala. Lesions of the right medial amygdala, when performed on diestrus-1, resulted in a significant decrease in the number of rats ovulating compared to controls (4/8 vs. 8/8, p rats with lesions of the right medial amygdala. However, sequential injections of PMSG-hCG did result in ovulation by all members of a group of lesioned animals. In this last condition a significant decrease in the number of ova shed by the right ovary was found compared to animals in the lesion-only condition (1.5 +/- 0.5 vs. 6.0 +/- 1.5, p cycle.

  6. Deficiency of the intestinal growth factor, glucagon-like peptide 2, in the colon of SCID mice with inflammatory bowel disease induced by transplantation of CD4+ T cells

    DEFF Research Database (Denmark)

    Schmidt, P T; Hartmann, B; Bregenholt, S

    2000-01-01

    Glucagon-like peptide 2 (GLP-2) is produced in endocrine L-cells of the intestinal mucosa. Recently, GLP-2 was found to stimulate intestinal mucosal growth. Our objective was to study the content of GLP-2 in the large intestine in a murine model of T-cell-induced inflammatory bowel disease....

  7. Virtual lesions of the inferior parietal cortex induce fast changes of implicit religiousness/spirituality.

    Science.gov (United States)

    Crescentini, Cristiano; Aglioti, Salvatore M; Fabbro, Franco; Urgesi, Cosimo

    2014-05-01

    Religiousness and spirituality (RS) are two ubiquitous aspects of human experience typically considered impervious to scientific investigation. Nevertheless, associations between RS and frontoparietal neural activity have been recently reported. However, much less is known about whether such activity is causally involved in modulating RS or just epiphenomenal to them. Here we combined two-pulse (10 Hz) Transcranial Magnetic Stimulation (TMS) with a novel, ad-hoc developed RS-related, Implicit Association Test (IAT) to investigate whether implicit RS representations, although supposedly rather stable, can be rapidly modified by a virtual lesion of inferior parietal lobe (IPL) and dorsolateral prefrontal cortex (DLPFC). A self-esteem (SE) IAT, focused on self-concepts nonrelated to RS representations, was developed as control. A specific increase of RS followed inhibition of IPL demonstrating its causative role in inducing fast plastic changes of religiousness/spirituality. In contrast, DLPFC inhibition had more widespread effects probably reflecting a general role in the acquisition or maintenance of task-rules or in controlling the expression of self-related representations not specific to RS. Copyright © 2014 Elsevier Ltd. All rights reserved.

  8. Photoreactivation reverses ultraviolet radition induced premutagenic lesions leading to frameshift mutations in Escherichia coli

    International Nuclear Information System (INIS)

    Yamamoto, Kazuo

    1985-01-01

    The effect of photoreactivation of the ultraviolet radiation induced reversion of a trpE9777 frameshift mutation was studied in a uvr A6 derivative of Escherichia coli K12. Two different photoreactivation treatments were used, one providing a single flash of photoreactivating light and another providing 10 min of light from fluorescent lamps. The reversion frequency of the trpE9777 frameshift mutation was strongly reduced when subsueqently exposed to visible light. The dose modification factor (the ratio of equally effective doses), for cells challenged with single-flash photoreactivation, for survival and induction of reversion to Trp + was 3.6 and 3.4, respectively. UV induction of RecA protein synthesis was not reversed by a single flash of photoreactivation. The dose modification factor for 10 min of fluorescent lamp photoreactivation for survival and for induction of reversion to Trp + was 6.5 and 6.3, respectively. The dose modification factor for 10 min of photoreactivation for induction of RecA protein was 1.7-2.5. Photoreactivation decreased the reversion of trpE9777 and increased survival to the same extent. We concluded that cyclobutyl pyrimidine dimers are the premutagenic lesions of UV mutagenesis of the trpE9777 allele in a uvr A6 background. (orig.)

  9. Surgical therapy of radiation-induced lesions of the colon and rectum

    International Nuclear Information System (INIS)

    Miholic, J.; Schwarz, C.; Moeschl, P.

    1988-01-01

    Thirty-six operations for late sequelae of radiotherapy were carried out in 31 patients from 1971 to 1986. The most frequent indications for surgery were stricture (58 percent) and fistula (29 percent). In the first 8 year period from 1971 through 1978, 13 of 14 operations were diversions (colostomy or by-pass). From 1979 through 1986, a more aggressive approach prevailed. Only 32 percent of the operations were diversions. This more aggressive strategy was accompanied by a decrease of the postoperative mortality rate from 21 percent through 1978 to 0 in the later period. The overall complication rate was 23 percent. Complications were relatively more frequent after two-layer sutured or stapled anastomoses and after resection or fistula closure without temporary colostomy. We conclude that in radiation-induced colonic and rectal lesions, diversion should be performed in patients with unproved cure of disease or tumor persistence. Resection and fistula closure can be carried out safely, and a temporary colostomy is strongly recommended

  10. Laser-induced fluorescence studies of premalignant and benign lesions in the female genital tract

    Science.gov (United States)

    af Klinteberg, Claes; Wang, Ingrid; Lindquist, Charlotta; Vaitkuviene, Aurelija; Svanberg, Katarina

    1997-12-01

    Laser-induced fluorescence (LIF) was studied in vivo from premalignant and benign lesions in the female genital tract, in particular the cervix. The aim of the study was to investigate the possibilities to differentiate cervical intraepithelial neoplasia (CIN) from normal tissue by means of two different fluorescence modalities. Most of the patients were given a low dose (5 mg/kg bw) of (delta) -amino levulinic acid (ALA). The ALA was orally administered 2 - 4 hours prior to the investigation. During this time, the ALA is transformed to the strongly fluorescent protoporphyrin IX (PpIX) via the haem cycle. Excitation light with a wavelength of 405 nm was used to excite the PpIX fluorescence. Excess amounts of PpIX were accumulated preferentially in diseased tissue. However, the variability in the PpIX accumulation from patient to patient was large. By using excitation light at 337 nm, the endogenous fluorophores are more efficiently excited. Therefore, this excitation modality was exploited for studying spectral characteristics of the autofluorescence in different tissue types. The spectra obtained were evaluated by forming fluorescence intensity ratios. The tissue types were grouped according to the histopathological examination. A correlation with the fluorescence ratios was performed. Some problems with the classification remain, mostly due to the difficulties in obtaining histopathologic evaluation of the biopsies at the exact location of the LIF measurements.

  11. Learning tasks as a possible treatment for DNA lesions induced by oxidative stress in hippocampal neurons

    Institute of Scientific and Technical Information of China (English)

    DragoCrneci; Radu Silaghi-Dumitrescu

    2013-01-01

    Reactive oxygen species have been implicated in conditions ranging from cardiovascular dysfunc-tion, arthritis, cancer, to aging and age-related disorders. The organism developed several path-ways to counteract these effects, with base excision repair being responsible for repairing one of the major base lesions (8-oxoG) in al organisms. Epidemiological evidence suggests that cognitive stimulation makes the brain more resilient to damage or degeneration. Recent studies have linked enriched environment to reduction of oxidative stressin neurons of mice with Alzheimer’s dis-ease-like disease, but given its complexity it is not clear what specific aspect of enriched environ-ment has therapeutic effects. Studies from molecular biology have shown that the protein p300, which is a transcription co-activator required for consolidation of memories during specific learning tasks, is at the same time involved in DNA replication and repair, playing a central role in the long-patch pathway of base excision repair. Based on the evidence, we propose that learning tasks such as novel object recognition could be tested as possible methods of base excision repair faci-litation, hence inducing DNA repair in the hippocampal neurons. If this method proves to be effective, it could be the start for designing similar tasks for humans, as a behavioral therapeutic complement to the classical drug-based therapy in treating neurodegenerative disorders. This review presents the current status of therapeutic methods used in treating neurodegenerative diseases induced by reactive oxygen species and proposes a new approach based on existing data.

  12. No interaction between X-ray induced lesions in maternal and paternal chromosomes in inseminated eggs of Drosophila melanogaster

    International Nuclear Information System (INIS)

    Wuergler, F.E.; Graf, U.; Jeanneret, P.

    1978-01-01

    X-ray induced premutational lesions persist in mature gametes of drosophila until fertilization. Repairable lesions in sperm and oocyte chromosomes are repaired exclusively by maternal repair systems in the inseminated egg. Interactions between irradiated genomes in inseminated eggs might result in additional lethality if breaks induced in separate nuclei, which would normally be repaired, could interact to form dicentric chromosomes. Adult drosophila flies were X-irradiated (up to 5 kR), individual females crossed to three or four males, and the dose-response curves for dominant lethals (embryonic lethality) compared. The results indicate thet the potentially lethal damage present in irradiated sperm chromosomes was expressed independently of whether or not the oocyte was also irradiated. There were no (or only very few) interactions between maternal and paternal chromosome complements, and the maternal repair systems acting on radiation-induced chromosome breaks in sperm were resistant to X-rays. (U.K.)

  13. A probiotic strain of L. acidophilus reduces DMH-induced large intestinal tumors in male Sprague-Dawley rats.

    Science.gov (United States)

    McIntosh, G H; Royle, P J; Playne, M J

    1999-01-01

    Probiotic bacteria strains were examined for their influence on 1,2-dimethylhydrazine (DMH)-induced intestinal tumors in 100 male Sprague-Dawley rats. Lactobacillus acidophilus (Delvo Pro LA-1), Lactobacillus rhamnosus (GG), Bifidobacterium animalis (CSCC1941), and Streptococcus thermophilus (DD145) strains were examined for their influence when added as freeze-dried bacteria to an experimental diet based on a high-fat semipurified (AIN-93) rodent diet. Four bacterial treatments were compared: L. acidophilus, L. acidophilus + B. animalis, L. rhamnosus, and S. thermophilus, the bacteria being added daily at 1% freeze-dried weight (10(10) colony-forming units/g) to the diet. Trends were observed in the incidence of rats with large intestinal tumors for three treatments: 25% lower than control for L. acidophilus, 20% lower for L. acidophilus + B. animalis and L. rhamnosus treatments, and 10% lower for S. thermophilus. Large intestinal tumor burden was significantly lower for treated rats with L. acidophilus than for the control group (10 and 3 tumors/treatment group, respectively, p = 0.05). Large intestinal tumor mass index was also lower for the L. acidophilus treatment than for control (1.70 and 0.10, respectively, p L. acidophilus, no adenocarcinomas were present in the colons. Pulsed-field gel electrophoresis of bacterial chromosomal DNA fragments was used to differentiate introduced (exogenous) bacterial strains from indigenous bacteria of the same genera present in the feces. Survival during gut passage and displacement of indigenous lactobacilli occurred with introduced L. acidophilus and L. rhamnosus GG during the probiotic treatment period. However, introduced strains of B. animalis and S. thermophilus were not able to be isolated from feces. It is concluded that this strain of L. acidophilus supplied as freeze-dried bacteria in the diet was protective, as seen by a small but significant inhibition of tumors within the rat colon.

  14. Comparative characteristic of transmembrane currents and caffeine-induced responses of intact and irradiated small intestine smooth muscle cells

    International Nuclear Information System (INIS)

    Stepanov, Yu.V.; Gordienko, D.V.; Preobrazhenskaya, T.D.; Stepanova, L.I.; Vojtsitskij, V.M.

    1994-01-01

    A comparative investigation of transmembrane ion currents and caffeine-induced responses of single smooth muscle cells isolated from the circular layer of rat small intestine was curried out by the method of 'patch-clamp'. No reliable difference in potential-dependent and amplitude-kinetic characteristics of transmembrane ion currents in cells of intact and irradiated with dose of 3 Gy rats was revealed. In cells of irradiated animals external application of caffeine (4 mM) was not accompanied by strong quick-inactivated transient Ca 2+ -dependent potassium current as in control

  15. The circadian rhythm for the number and sensitivity of radiation-induced apoptosis in the crypts of mouse small intestine

    International Nuclear Information System (INIS)

    Ijiri, K.; Potten, C.S.

    1990-01-01

    Survival curves were constructed from dose-incidence curves for apoptosis in the crypts of mouse small intestine, using the number of apoptotic cells after high doses (N M ) as maximum cell population size. The mean lethal doses (D 0 ) for the dose range 0-0.5 Gy were calculated for each time of day. A circadian rhythm in both D 0 and N M values was detected, indicating that both the number and sensitivity of radiation-induced apoptosis were changing throughout the day. (author)

  16. Vasoactive intestinal polypeptide induces glycogenolysis in mouse cortical slices: a possible regulatory mechanism for the local control of energy metabolism.

    OpenAIRE

    Magistretti, P J; Morrison, J H; Shoemaker, W J; Sapin, V; Bloom, F E

    1981-01-01

    Mouse cerebral cortex slices will synthesize [3H]glycogen in vitro. Vasoactive intestinal polypeptide (VIP) stimulates the enzymatic breakdown of this [3H]glycogen. The concentration giving 50% of maximum effectiveness (EC50) is 26 nM. Under the same experimental conditions norepinephrine also induces a concentration-dependent [3H]glycogen hydrolysis with an EC50 of 500 nM. The effect of VIP is not mediated by the release of norepinephrine because it is not blocked by the noradrenergic antago...

  17. Expression of p53, inducible nitric oxide synthase and vascular endothelial growth factor in gastric precancerous and cancerous lesions: correlation with clinical features

    International Nuclear Information System (INIS)

    Feng, Chang Wei; Wang, Li Dong; Jiao, Lian Hua; Liu, Bin; Zheng, Shu; Xie, Xin Ji

    2002-01-01

    The growth and metastasis of tumors depend on the development of an adequate blood supply via angiogenesis. Recent studies indicate that the inducible nitric oxide synthase (iNOS), vascular endothelial growth factor (VEGF) and the tumor suppressor p53 are fundamental play-markers of the angiogenic process. Overexpression of iNOS and VEGF has been shown to induce angiogenesis in tumors. P53 suppresses angiogenesis by down-regulating VEGF and iNOS. The correlation of expression of p53, VEGF and iNOS and clinical features in gastric carcinogenesis, however, has not been well characterized. The expression of p53, iNOS and VEGF in gastric precancerous and cancerous lesions and its relation with the clinical features was determined with immunohistochemistry (avidin-biotin-peroxidase complex method) on 55 randomly selected GC patients and 60 symptom-free subjects from the mass survey in the high-incidence area for GC in Henan, northern China. The positive immunostainig rates for p53, iNOS and VEGF in gastric carcinomas were 51%, 44% and 51%, respectively, and correlated well with TNM stages, but did not show significant difference among the groups with different degrees of gastric wall invasion depth by GC. A positive immunostaining reaction for the iNOS protein was significantly correlated with lymph node metastasis (p = 0.019; Spearman correlation coefficient). P53 protein accumulation was higher in the poorly-differentiated gastric carcinoma than in well-differentiated one. In gastric biopsies, no positive immunosatining was observed for p53, iNOS and VEGF in the histologically normal tissue and chronic superficial gastritis (CSG). However, p53, iNOS and VEGF positive immunostaining was observed in the tissues with different severities of lesions of chronic atrophic gastritis (CAG), intestinal metaplasia (IM) and dysplasia (DYS), and the positive rates increased with the lesion progression from CAG to IM to DYS. A high coincidental positive and negative immunostaining

  18. Effects of Pharmacological Inhibition and Genetic Deficiency of Plasminogen Activator Inhibitor-1 in Radiation-Induced Intestinal Injury

    International Nuclear Information System (INIS)

    Abderrahmani, Rym; Francois, Agnes; Buard, Valerie; Benderitter, Marc; Sabourin, Jean-Christophe; Crandall, David L.; Milliat, Fabien

    2009-01-01

    Purpose: To investigate effects of plasminogen activator inhibitor 1 (PAI-1) genetic deficiency and pharmacological PAI-1 inhibition with PAI-039 in a mouse model of radiation-induced enteropathy. Methods and Materials: Wild-type (Wt) and PAI-1 -/- knockout mice received a single dose of 19 Gy to an exteriorized localized intestinal segment. Sham and irradiated Wt mice were treated orally with 1 mg/g of PAI-039. Histological modifications were quantified using a radiation injury score. Moreover, intestinal gene expression was monitored by real-time PCR. Results: At 3 days after irradiation, PAI-039 abolished the radiation-induced increase in the plasma active form of PAI-1 and limited the radiation-induced gene expression of transforming growth factor β1 (TGF-β1), CTGF, PAI-1, and COL1A2. Moreover, PAI-039 conferred temporary protection against early lethality. PAI-039 treatment limited the radiation-induced increase of CTGF and PAI-1 at 2 weeks after irradiation but had no effect at 6 weeks. Radiation injuries were less severe in PAI-1 -/- mice than in Wt mice, and despite the beneficial effect, 3 days after irradiation, PAI-039 had no effects on microscopic radiation injuries compared to untreated Wt mice. Conclusions: A genetic deficiency of PAI-1 is associated with amelioration of late radiation enteropathy. Pharmacological inhibition of PAI-1 by PAI-039 positively impacts the early, acute phase increase in plasma PAI-1 and the associated radiation-induced gene expression of inflammatory/extracellular matrix proteins. Since PAI-039 has been shown to inhibit the active form of PAI-1, as opposed to the complete loss of PAI-1 in the knockout animals, these data suggest that a PAI-1 inhibitor could be beneficial in treating radiation-induced tissue injury in acute settings where PAI-1 is elevated.

  19. Endoglin negatively regulates transforming growth factor beta1-induced profibrotic responses in intestinal fibroblasts.

    LENUS (Irish Health Repository)

    Burke, J P

    2012-02-01

    BACKGROUND: Fibroblasts isolated from strictures in Crohn\\'s disease (CD) exhibit reduced responsiveness to stimulation with transforming growth factor (TGF) beta1. TGF-beta1, acting through the smad pathway, is critical to fibroblast-mediated intestinal fibrosis. The membrane glycoprotein, endoglin, is a negative regulator of TGF-beta1. METHODS: Intestinal fibroblasts were cultured from seromuscular biopsies of patients undergoing intestinal resection for CD strictures or from control patients. Endoglin expression was assessed using confocal microscopy, flow cytometry and western blot. The effect of small interfering (si) RNA-mediated knockdown and plasmid-mediated overexpression of endoglin on fibroblast responsiveness to TGF-beta1 was assessed by examining smad phosphorylation, smad binding element (SBE) promoter activity, connective tissue growth factor (CTGF) expression and ability to contract collagen. RESULTS: Crohn\\'s stricture fibroblasts expressed increased constitutive cell-surface and whole-cell endoglin relative to control cells. Endoglin co-localized with filamentous actin. Fibroblasts treated with siRNA directed against endoglin exhibited enhanced TGF-beta1-mediated smad-3 phosphorylation, and collagen contraction. Cells transfected with an endoglin plasmid did not respond to TGF-beta1 by exhibiting SBE promoter activity or producing CTGF. CONCLUSION: Fibroblasts from strictures in CD express increased constitutive endoglin. Endoglin is a negative regulator of TGF-beta1 signalling in the intestinal fibroblast, modulating smad-3 phosphorylation, SBE promoter activity, CTGF production and collagen contraction.

  20. Mixed Lactobacillus plantarum Strains Inhibit Staphylococcus aureus Induced Inflammation and Ameliorate Intestinal Microflora in Mice.

    Science.gov (United States)

    Ren, Dayong; Gong, Shengjie; Shu, Jingyan; Zhu, Jianwei; Rong, Fengjun; Zhang, Zhenye; Wang, Di; Gao, Liangfeng; Qu, Tianming; Liu, Hongyan; Chen, Ping

    2017-01-01

    Objective . Staphylococcus aureus is an important pathogen that causes intestinal infection. We examined the immunomodulatory function of single and mixed Lactobacillus plantarum strains, as well as their impacts on the structure of the microbiome in mice infected with Staphylococcus aureus . The experiment was divided into three groups: protection, treatment, and control. Serum IFN- γ and IL-4 levels, as well as intestinal sIgA levels, were measured during and 1 week after infection with Staphylococcus aureus with and without Lactobacillus plantarum treatment. We used 16s rRNA tagged sequencing to analyze microbiome composition. IFN- γ /IL-4 ratio decreased significantly from infection to convalescence, especially in the mixed Lactobacillus plantarum group. In the mixed Lactobacillus plantarum group the secretion of sIgA in the intestine of mice (9.4-9.7 ug/mL) was significantly higher than in the single lactic acid bacteria group. The dominant phyla in mice are Firmicutes , Bacteroidetes , and Proteobacteria . Treatment with mixed lactic acid bacteria increased the anti-inflammatory factor and the secretion of sIgA in the intestine of mice infected with Staphylococcus aureus and inhibited inflammation.

  1. Carbachol ameliorates lipopolysaccharide-induced intestinal epithelial tight junction damage by down-regulating NF-{kappa}{beta} and myosin light-chain kinase pathways

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, Ying [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China); Li, Jianguo, E-mail: 2010lijianguo@sina.cn [Department of Anesthesia, Critical Care Medicine and Emergency Medicine Center, Zhongnan Hospital, Wuhan University, Wuhan 430071, Hubei Province, People' s Republic of China (China)

    2012-11-16

    Highlights: Black-Right-Pointing-Pointer Carbachol reduced the lipopolysaccharide-induced intestinal barrier breakdown. Black-Right-Pointing-Pointer Carbachol ameliorated the lipopolysaccharide-induced ileal tight junction damage. Black-Right-Pointing-Pointer Carbachol prevented the LPS-induced NF-{kappa}{beta} and myosin light-chain kinase activation. Black-Right-Pointing-Pointer Carbachol exerted its beneficial effects in an {alpha}7 nicotinic receptor-dependent manner. -- Abstract: Carbachol is a cholinergic agonist that protects the intestines after trauma or burn injury. The present study determines the beneficial effects of carbachol and the mechanisms by which it ameliorates the lipopolysaccharide (LPS)-induced intestinal barrier breakdown. Rats were injected intraperitoneally with 10 mg/kg LPS. Results showed that the gut barrier permeability was reduced, the ultrastructural disruption of tight junctions (TJs) was prevented, the redistribution of zonula occludens-1 and claudin-2 proteins was partially reversed, and the nuclear factor-kappa beta (NF-{kappa}{beta}) and myosin light-chain kinase (MLCK) activation in the intestinal epithelium were suppressed after carbachol administration in LPS-exposed rats. Pretreatment with the {alpha}7 nicotinic acetylcholine receptor ({alpha}7nAchR) antagonist {alpha}-bungarotoxin blocked the protective action of carbachol. These results suggested that carbachol treatment can protect LPS-induced intestinal barrier dysfunction. Carbachol exerts its beneficial effect on the amelioration of the TJ damage by inhibiting the NF-{kappa}{beta} and MLCK pathways in an {alpha}7nAchR-dependent manner.

  2. Nitric oxide (NO) production in mammalian non-tumorigenic epithelial cells of the small intestine and macrophages induced by individual strains of lactobacilli and bifidobacteria

    DEFF Research Database (Denmark)

    Pipenbaher, Natasa; Møller, Peter Lange; Dolinsek, Jan

    2009-01-01

    and absence of interferon gamma (INF-¿). Production of NO in intestinal epithelium was stimulated by individual strains of lactobacilli without INF-¿ priming. While none of the tested bifidobacteria were capable of inducing NO production, most constitutively secreted NO. Most tested strains induced...

  3. EXERCISE-INDUCED SYMPATHETIC FFA MOBILIZATION IN VMH-LESIONED RATS IS NORMALIZED BY FASTING

    NARCIS (Netherlands)

    Balkan, B.; Dijk, G. van; Strubbe, J.H.; Bruggink, J.E.; Steffens, A.B.

    This study investigates whether reduced sympathetic responses during physical exercise in ventromedial hypothalamus (VMH)-lesioned obese rats are the direct result of damage to hypothalamic circuits or a secondary effect of the altered metabolism in obesity. Obese, VMH-lesioned rats and lean

  4. The role of inducible Nitric Oxide Synthase in teeth periapical lesions immunopathogenesis caused by Enterococcus faecalis

    Directory of Open Access Journals (Sweden)

    Tamara Yuanita

    2013-03-01

    Full Text Available Background: Periapical lesions, are characterized by an immune response to the invading bacteria consequences periapical bone destruction. In root canal treatment failure was found Enterococcus faecalis (E. faecalis as most species. iNOS found an important role in protection against infection, plays vital roles in fighting pathogens and contributing to disease pathology. Purpose: This study was to observed the role of iNOS in teeth periapical lessions immunopathogenesis caused by E. faecalis. Methods: The randomized post-only control group design used in this study, This study used 24 Wistar rats, were divided into three groups (each group consisted of 8 rats, as negative controls group is a normal teeth, in the positive controls group was made by drilling the upper right first molar to penetrate the dental pulp and was induced with 10µl BHI-b then filled with Glass Ionomer Cement (GIC and the treatment group, after drilling the teeth, then inoculated with E. faecalis ATCC 29212 106 CFU into 10µl BHI-b then filled with GIC to prevent contamination. It takes 21 days to get periapical lesions and rat were sacrificed, and then the expression of iNOS was measured. Results: Statistical analysis using ANOVA found a significant differenced between control and treatment groups (p<0.05. Conclusion: This study concluded that iNOS role in teeth periapical lesions immunopathogenesis caused by E. faecalis.Latar belakang: Lesi periapikal merupakan hasil suatu respon imun untuk melawan invasi bakteri yang mengakibatkan destruksi tulang periapikal. Pada perawatan saluran akar yang mengalami kegagalan ditemukan Enterococcus faecalis sebagai spesies terbanyak. iNOS berperan penting untuk proteksi terhadap bakteri, mempunyai peran yang vital untuk melawan patogen dan berkonstribusi secara patologik untuk menyebabkan suatu penyakit. Tujuan: Penelitian ini bertujuan untuk mengobservasi peran iNOS secara imunohistokimia pada lesi periapikal tikus Wistar. Metode

  5. Laser induced biostimulation: A possible healing prospect in endo-perio lesion

    Directory of Open Access Journals (Sweden)

    Mithra N Hegde

    2012-01-01

    Full Text Available The health of the tooth is governed by both endodontic tissue and periodontal apparatus. "Endo-perio lesion" is the term used to describe the lesions in which inflammatory products involves both pulpal and periodontal tissues in varying degrees. The disease of endodontium may lead to the involvement of the periodontium and vice versa. Endo-perio lesions are the clinical conditions that are often difficult to diagnose and persistent if not treated appropriately. Lasers have been used successfully in endodontic as well as periodontal procedures. With endodontic treatment alone, only part of the lesion will heal to the level of the secondary periodontal lesion. Overall prognosis depends upon the severity of periodontal damage and the efficacy of the periodontal treatment. Laser can be considered as an efficacious tool and an adjunct to conventional periodontal therapy both for its decontaminating and biostimulating effects.

  6. The role of food for the formation and prevention of gastrointestinal lesions induced by aspirin in cats.

    Science.gov (United States)

    Satoh, Hiroshi; Amagase, Kikuko; Takeuchi, Koji

    2013-10-01

    The effects of feeding conditions (fasted or fed) and dietary fiber (DF) in the diet on gastrointestinal (GI) damage induced by aspirin (ASA) were examined in cats. Plain ASA (P-ASA, 20 mg/kg) or one enteric-coated ASA tablet (EC-ASA, containing 100 mg ASA) was administered p.o. once daily for 3 or 7 days just after morning meal, 3 h after the evening meal, or in the morning without a morning meal (fasted). Several types of diet, dry food (DRY, DF: 2.8 %), canned food (CAN, DF: 0.4 %), and diets with added cellulose or pectin were provided twice daily. P-ASA or EC-ASA administered just after feeding of DRY caused marked lesions in the GI tract, although EC-ASA did not produce any lesions in the stomach. GI damage was markedly decreased when ASA was administered 3 h after the evening meal. The induction of lesions by EC-ASA was markedly decreased in cats that ate CAN, but lesions were induced in cats fed CAN with added cellulose (6 %). The addition of pectin (6 %) to the DRY markedly decreased the induction of lesions by EC-ASA. The results indicate that the induction of GI lesions by ASA was highly dependent on the feeding conditions and DF. To minimize the induction of GI damage, it would be better to take ASA 3 h after the evening meal, or after consuming diets that contain low amounts of insoluble DF and high amounts of soluble DF.

  7. Hydrolysed inulin alleviates the azoxymethane-induced preneoplastic aberrant crypt foci by altering selected intestinal microbiota in Sprague-Dawley rats.

    Science.gov (United States)

    Pattananandecha, Thanawat; Sirilun, Sasithorn; Duangjitcharoen, Yodsawee; Sivamaruthi, Bhagavathi Sundaram; Suwannalert, Prasit; Peerajan, Sartjin; Chaiyasut, Chaiyavat

    2016-09-01

    Context Inulin, a non-digestible carbohydrate isolated from Helianthus tuberosus L. (Asteraceae), has been shown to alter the gut beneficial bacteria including Lactobacillus spp. and Bifidobacteria. Inulin also influences the activities of intestinal microbiota that could prevent the colon cancer development. Objective This study determines the effect of hydrolysed inulin with different degrees of polymerisation on alteration of intestinal microbiota and their activities on azoxymethane (AOM)-induced preneoplastic aberrant crypt foci (ACF) in rats. Materials and methods Seventy-two male Sprague-Dawley rats were randomly divided into six groups (three control and three AOM-treated groups) and the animal were fed with either a normal diet or diet containing 10% of long-chain inulin (InuL) or short-chain inulin (InuS), respectively, for 17 weeks. Colon cancer was induced in rats by injecting AOM subcutaneously at the 8th and 9th week of the study period. At the end of the experiment, cecal contents of rats were examined for selected microbiota, organic acids, putrefactive compounds and microbial enzymes. ACF formation was microscopically examined. Results The inulin diets significantly increased the weight and decreased the pH of the caecal content. The rats fed with InuL-supplemented diet showed approximately 2.9- and 6.8-fold increases in the biomass of Lactobacillus spp. and Bifidobacteria, respectively. Naive and AOM-treated rats fed with inulin-supplemented diet showed ∼1.3- and ∼2.2-fold decreases in the biomass of Escherichia coli and Salmonella enterica serovar Typhi, respectively. Inulins significantly decreased the colonic concentration of phenol, p-cresol and indole. Reduction in the activity of microbial enzymes such as β-glucuronidase, azoreductase and nitroreductase were observed in inulin-treated animals. Reduction in the ACF formation has been observed in inulin-treated groups. Discussion and conclusion The present study demonstrates that dietary

  8. Hyperactivity induced by stimulation of separate dopamine D-1 and D-2 receptors in rats with bilateral 6-OHDA lesions.

    Science.gov (United States)

    Arnt, J

    1985-08-26

    The effects of DA agonists and antagonists with different dopamine (DA) D-1 and D-2 receptor selectivity have been studied in rats with bilateral 6-OHDA lesions. The D-1 agonist SK & F 38393, the D-2 agonist pergolide and the mixed agonist apomorphine all induced marked hyperactivity in lesioned rats in doses which were without stimulant effect in sham-operated animals. The hyperactivity induced by SK & F 38393 was blocked by the DA D-1 antagonist SCH 23390, but unaffected by the D-2 antagonists spiroperidol or clebopride. Pergolide-induced hyperactivity showed the reverse selectivity. The mixed D-1/D-2 antagonists, cis(Z)-flupentixol and cis(Z)-clopenthixol, however blocked the effect of both agonists. Apomorphine-induced hyperactivity was neither blocked by selective D-1 nor D-2 antagonists, but was dose-dependently inhibited by cis(Z)-flupentixol and cis(Z)-clopenthixol. Potent blockade was also obtained by combined treatment with SCH 23390 and spiroperidol, indicating the need of blocking both D-1 and D-2 receptors simultaneously. The results indicate that D-1 and D-2 receptor function can be independently manipulated in denervated rats and they confirm similar results obtained in rats with unilateral 6-OHDA lesions using circling behaviour.

  9. Metagenomic analyses of alcohol induced pathogenic alterations in the intestinal microbiome and the effect of Lactobacillus rhamnosus GG treatment.

    Directory of Open Access Journals (Sweden)

    Lara Bull-Otterson

    Full Text Available Enteric dysbiosis plays an essential role in the pathogenesis of alcoholic liver disease (ALD. Detailed characterization of the alterations in the gut microbiome is needed for understanding their pathogenic role in ALD and developing effective therapeutic approaches using probiotic supplementation. Mice were fed liquid Lieber-DeCarli diet without or with alcohol (5% v/v for 6 weeks. A subset of mice were administered the probiotic Lactobacillus rhamnosus GG (LGG from 6 to 8 weeks. Indicators of intestinal permeability, hepatic steatosis, inflammation and injury were evaluated. Metagenomic analysis of the gut microbiome was performed by analyzing the fecal DNA by amplification of the V3-V5 regions of the 16S rRNA gene and large-scale parallel pyrosequencing on the 454 FLX Titanium platform. Chronic ethanol feeding caused a decline in the abundance of both Bacteriodetes and Firmicutes phyla, with a proportional increase in the gram negative Proteobacteria and gram positive Actinobacteria phyla; the bacterial genera that showed the biggest expansion were the gram negative alkaline tolerant Alcaligenes and gram positive Corynebacterium. Commensurate with the qualitative and quantitative alterations in the microbiome, ethanol caused an increase in plasma endotoxin, fecal pH, hepatic inflammation and injury. Notably, the ethanol-induced pathogenic changes in the microbiome and the liver were prevented by LGG supplementation. Overall, significant alterations in the gut microbiome over time occur in response to chronic alcohol exposure and correspond to increases in intestinal barrier dysfunction and development of ALD. Moreover, the altered bacterial communities of the gut may serve as significant therapeutic target for the prevention/treatment of chronic alcohol intake induced intestinal barrier dysfunction and liver disease.

  10. The histopathological comparison of L-carnitine with amifostine for protective efficacy on radiation-induced acute small intestinal toxicity

    Directory of Open Access Journals (Sweden)

    Murat Caloglu

    2012-01-01

    Full Text Available Background: The aim of the study was to compare the protective efficacy of l-carnitine (LC to amifostine on radiation-induced acute small intestine damage. Materials and Methods: Thirty, 4-week-old Wistar albino rats were randomly assigned to four groups - Group 1: control (CONT, n = 6, Group 2: irradiation alone (RT, n = 8, Group 3: amifostine plus irradiation (AMI+RT, n = 8, and Group 4: l-Carnitine plus irradiation (LC+RT, n = 8. The rats in all groups were irradiated individually with a single dose of 20 Gy to the total abdomen, except those in CONT. LC (300 mg/kg or amifostine (200 mg/kg was used 30 min before irradiation. Histopathological analysis of small intestine was carried out after euthanasia. Results: Pretreatment with amifostine reduced the radiation-induced acute degenerative damage (P = 0.009 compared to the RT group. Pretreatment with LC did not obtain any significant difference compared to the RT group. The vascular damage significantly reduced in both of the AMI+RT (P = 0.003 and LC+RT group (P = 0.029 compared to the RT group. The overall damage score was significantly lower in the AMI+RT group than the RT group (P = 0.009. There was not any significant difference between the LC+RT and RT group. Conclusions: Amifostine has a marked radioprotective effect against all histopathological changes on small intestinal tissue while LC has limited effects which are mainly on vascular structure.

  11. An in vitro comparison of quantitative light-induced fluorescence-digital and spectrophotometer on monitoring artificial white spot lesions.

    Science.gov (United States)

    Kim, Hee Eun; Kim, Baek-Il

    2015-09-01

    The aim of this study was to evaluate the efficacy of quantitative light-induced fluorescence-digital (QLF-D) compared to a spectrophotometer in monitoring progression of enamel lesions. To generate artificial caries with various severities of lesion depths, twenty bovine specimens were immersed in demineralizing solution for 40 days. During the production of the lesions, repeat measurements of fluorescence loss (ΔF) and color change (ΔE) were performed in six distinct stages after the demineralization of the specimens: after 3, 5, 10, 20, 30, and 40 days of exposure to the demineralizing solution. Changes in the ΔF values in the lesions were analyzed using the QLF-D, and changes in the ΔE values in lesions were analyzed using a spectrophotometer. The repeated measures ANOVA of ΔF and ΔE values were used to determine whether there are significant differences at different exposure times in the demineralizing solution. Spearman's rank correlation coefficient was analyzed between ΔF and ΔE. The ΔF values significantly decreased based on the demineralizing period (pmonitoring color changes. Our findings demonstrate that QLF-D are a more efficient and stable tool for early caries detection. Copyright © 2015 Elsevier B.V. All rights reserved.

  12. Gypenosides attenuate the development of L-DOPA-induced dyskinesia in 6-hydroxydopamine-lesioned rat model of Parkinson's disease.

    Science.gov (United States)

    Shin, Keon Sung; Zhao, Ting Ting; Park, Keun Hong; Park, Hyun Jin; Hwang, Bang Yeon; Lee, Chong Kil; Lee, Myung Koo

    2015-04-21

    Gypenosides (GPS) and ethanol extract of Gynostemma pentaphyllum (GP-EX) show anxiolytic effects on affective disorders in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-lesioned mouse model of Parkinson's disease (PD). Long-term administration of L-3,4-dihydroxyphenylalanine (L-DOPA) leads to the development of severe motor side effects such as L-DOPA-induced-dyskinesia (LID) in PD. The present study investigated the effects of GPS and GP-EX on LID in a 6-hydroxydopamine (6-OHDA)-lesioned rat model of PD. Daily administration of L-DOPA (25 mg/kg) in the 6-OHDA-lesioned rat model of PD for 22 days induced expression of LID, which was determined by the body and locomotive AIMs scores and contralateral rotational behaviors. However, co-treatments of GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg) with L-DOPA significantly attenuated the development of LID without compromising the anti-parkinsonian effects of L-DOPA. In addition, the increases in ∆FosB expression and ERK1/2 phosphorylation in 6-OHDA-lesioned rats induced by L-DOPA administration were significantly reduced by co-treatment with GPS (25 and 50 mg/kg) or GP-EX (50 mg/kg). These results suggest that GPS (25 and 50 mg/kg) and GP-EX (50 mg/kg) effectively attenuate the development of LID by modulating the biomarker activities of ∆FosB expression and ERK1/2 phosphorylation in the 6-OHDA-lesioned rat model of PD. GPS and GP-EX will be useful adjuvant therapeutics for LID in PD.

  13. Cannabidiol restores intestinal barrier dysfunction and inhibits the apoptotic process induced by Clostridium difficile toxin A in Caco-2 cells.

    Science.gov (United States)

    Gigli, Stefano; Seguella, Luisa; Pesce, Marcella; Bruzzese, Eugenia; D'Alessandro, Alessandra; Cuomo, Rosario; Steardo, Luca; Sarnelli, Giovanni; Esposito, Giuseppe

    2017-12-01

    Clostridium difficile toxin A is responsible for colonic damage observed in infected patients. Drugs able to restore Clostridium difficile toxin A-induced toxicity have the potential to improve the recovery of infected patients. Cannabidiol is a non-psychotropic component of Cannabis sativa, which has been demonstrated to protect enterocytes against chemical and/or inflammatory damage and to restore intestinal mucosa integrity. The purpose of this study was to evaluate (a) the anti-apoptotic effect and (b) the mechanisms by which cannabidiol protects mucosal integrity in Caco-2 cells exposed to Clostridium difficile toxin A. Caco-2 cells were exposed to Clostridium difficile toxin A (30 ng/ml), with or without cannabidiol (10 -7 -10 -9  M), in the presence of the specific antagonist AM251 (10 -7  M). Cytotoxicity assay, transepithelial electrical resistence measurements, immunofluorescence analysis and immunoblot analysis were performed in the different experimental conditions. Clostridium difficile toxin A significantly decreased Caco-2 cells' viability and reduced transepithelial electrical resistence values and RhoA guanosine triphosphate (GTP), bax, zonula occludens-1 and occludin protein expression, respectively. All these effects were significantly and concentration-dependently inhibited by cannabidiol, whose effects were completely abolished in the presence of the cannabinoid receptor type 1 (CB1) antagonist, AM251. Cannabidiol improved Clostridium difficile toxin A-induced damage in Caco-2 cells, by inhibiting the apoptotic process and restoring the intestinal barrier integrity, through the involvement of the CB1 receptor.

  14. Dotted collar placed around carotid artery induces asymmetric neointimal lesion formation in rabbits without intravascular manipulations

    Directory of Open Access Journals (Sweden)

    Kivelä Antti

    2012-10-01

    Full Text Available Abstract Background Neointimal formation in atherosclerosis has been subject for intense research. However, good animal models mimicking asymmetrical lesion formation in human subjects have been difficult to establish. The aim of this study was to develop a model which would lead to the formation of eccentric lesions under macroscopically intact non-denuded endothelium. Methods We have developed a new collar model where we placed two cushions or dots inside the collar. Arterial lesions were characterized using histology and ultrasound methods. Results When this dotted collar was placed around carotid and femoral arteries it produced asymmetrical pressure on adventitia and a mild flow disturbance, and hence a change in shear stress. Our hypothesis was that this simple procedure would reproducibly produce asymmetrical lesions without any intraluminal manipulations. Intima/media ratio increased towards the distal end of the collar with the direction of blood flow under macroscopically intact endothelium. Macrophages preferentially accumulated in areas of the thickest neointima thus resembling early steps in human atherosclerotic plaque formation. Proliferating cells in these lesions and underlying media were scarce at eight weeks time point. Conclusion The improved dotted collar model produces asymmetrical human-like atherosclerotic lesions in rabbits. This model should be useful in studies regarding the pathogenesis and formation of eccentric atherosclerotic lesions.

  15. Baccaurea angulata fruit juice reduces atherosclerotic lesions in diet-induced Hypercholesterolemic rabbits.

    Science.gov (United States)

    Ibrahim, Muhammad; Ahmed, Idris Adewale; Mikail, Maryam Abimbola; Ishola, Afeez Adekunle; Draman, Samsul; Isa, Muhammad Lokman Md; Yusof, Afzan Mat

    2017-07-07

    Atherosclerosis is the most common disease of large and medium-sized arteries linked to oxidative stress, dyslipidemia as well as chronic inflammation. The aim of this study was to evaluate the potential health benefits of Baccaurea angulata (BA) fruit juice on the aorta of diet-induced hypercholesterolemic rabbits, to detect an accumulation of fatty streak and evaluate the percentage of atherosclerotic lesion accrued. Thirty-five healthy male adults New Zealand White rabbits were assigned to seven different groups. Four groups were fed 1% cholesterol diet and 0, 0.5, 1.0, and 1.5 mL of BA fruit juice per kg of rabbit daily (atherogenic groups), while the other three groups were fed commercial rabbit pellet and 0, 0.5, and 1.0 mL of juice per kg of rabbit daily (normocholesterolemic groups) for 90 days. The thoracic and abdominal aorta between the heart origin and bifurcation into iliac arteries of all the rabbits were carefully removed and analyzed accordingly. The supplementation of the high-cholesterol diet of hypercholesterolemic rabbits with only 0.5 mL BA/kg rabbit per day significantly (p < 0.001) improved aortic lipid profile, attenuated aortic fatty streak development and reduced intima thickening. Higher BA doses used (1.0 and 1.5 mL/kg rabbit per day) also significantly (p < 0.001) decreased further the development of aortic fatty streaks, reduced the thickening of the tunica intima layer and preserved endothelial healing following arterial injury. Therefore, BA fruit is a potential novel functional food with effective anti-inflammatory, anti-atherogenic and hypocholesterolemic activities.

  16. Changes in the carbohydrate-energy metabolism with radiation-induced intestine syndrome

    International Nuclear Information System (INIS)

    Kendysh, I.N.; Grozdov, S.P.

    1981-01-01

    A local exposure of the rat abdomen in a dose of 3.6 cC/kg decreases the oxygen uptake, oxidation of glucose and fatty acids, glucose tolerance and insulin resistance, and also causes a trend toward lactic acidosis. These changes in the carbohydrate-energy metabolism are normalized with the administration of insulin and dichloracetate, and they may be interpreted as consequences of a shock provoked by a massive predominant injury to the intestine [ru

  17. Total intermittent Pringle maneuver during liver resection can induce intestinal epithelial cell damage and endotoxemia.

    Directory of Open Access Journals (Sweden)

    Simon A W G Dello

    Full Text Available OBJECTIVES: The intermittent Pringle maneuver (IPM is frequently applied to minimize blood loss during liver transection. Clamping the hepatoduodenal ligament blocks the hepatic inflow, which leads to a non circulating (hepatosplanchnic outflow. Also, IPM blocks the mesenteric venous drainage (as well as the splenic drainage with raising pressure in the microvascular network of the intestinal structures. It is unknown whether the IPM is harmful to the gut. The aim was to investigate intestinal epithelial cell damage reflected by circulating intestinal fatty acid binding protein levels (I-FABP in patients undergoing liver resection with IPM. METHODS: Patients who underwent liver surgery received total IPM (total-IPM or selective IPM (sel-IPM. A selective IPM was performed by selectively clamping the right portal pedicle. Patients without IPM served as controls (no-IPM. Arterial blood samples were taken immediately after incision, ischemia and reperfusion of the liver, transection, 8 hours after start of surgery and on the first post-operative day. RESULTS: 24 patients (13 males were included. 7 patients received cycles of 15 minutes and 5 patients received cycles of 30 minutes of hepatic inflow occlusion. 6 patients received cycles of 15 minutes selective hepatic occlusion and 6 patients underwent surgery without inflow occlusion. Application of total-IPM resulted in a significant increase in I-FABP 8 hours after start of surgery compared to baseline (p<0.005. In the no-IPM group and sel-IPM group no significant increase in I-FABP at any time point compared to baseline was observed. CONCLUSION: Total-IPM in patients undergoing liver resection is associated with a substantial increase in arterial I-FABP, pointing to intestinal epithelial injury during liver surgery. TRIAL REGISTRATION: ClinicalTrials.gov NCT01099475.

  18. Fine needle aspiration cytology of radiation-induced changes in nonneoplastic breast lesions. Possible pitfalls in cytodiagnosis

    International Nuclear Information System (INIS)

    Peterse, J.L.; Thunnissen, F.B.; van Heerde, P.

    1989-01-01

    The range of radiation-induced changes in fine needle aspiration (FNA) smears of the breast is described. In 41 of more than 800 patients who underwent breast-conserving treatment, a palpable breast lesion developed, and FNA was performed. In six cases, a recurrent carcinoma was present. In the remaining cases, three patterns of nonneoplastic lesions could be discerned: epithelial atypia (14 cases), fat necrosis (10 cases) and poorly cellular smears without epithelial atypia or fat necrosis (13 cases). It is important to be familiar with the patterns of radiation-induced epithelial atypia, since such atypia may lead to a misdiagnosis of recurrent carcinoma. These atypical cells may show impressive anisocytosis and anisonucleosis; however, the nuclear/cytoplasmic ratio remains normal and an admixture of bipolar cells is present. Cell dissociation and necrotic cell debris, as often seen in breast cancer smears, were never encountered in FNA smears from radiated nonneoplastic breasts

  19. Prophylactic effect of rebamipide on aspirin-induced gastric lesions and disruption of tight junctional protein zonula occludens-1 distribution.

    Science.gov (United States)

    Suzuki, Takahiro; Yoshida, Norimasa; Nakabe, Nami; Isozaki, Yutaka; Kajikawa, Hirokazu; Takagi, Tomohisa; Handa, Osamu; Kokura, Satoshi; Ichikawa, Hiroshi; Naito, Yuji; Matsui, Hirofumi; Yoshikawa, Toshikazu

    2008-03-01

    Aspirin and nonsteroidal anti-inflammatory agents are known to induce gastroduodenal complications such as ulcer, bleeding, and dyspepsia. In this study, we examined the prophylactic effect of rebamipide, an anti-ulcer agent with free-radical scavenging and anti-inflammatory effect, on acidified aspirin-induced gastric mucosal injury in rats. In addition, we investigated the mucosal barrier functions disrupted by aspirin. Oral administration of acidified aspirin resulted in linear hemorrhagic erosions with increasing myeloperoxidase activity and thiobarbituric acid-reactive substance concentrations in the gastric mucosa. Rebamipide suppressed these acidified aspirin-induced gastric lesions and inflammatory changes significantly, and its protective effect was more potent in the case of repeated (twice daily for 3 days) treatment than single treatment before aspirin administration. Immunostaining of zonula occludens (ZO)-1, one of the tight junctional proteins, was strengthened in rat gastric mucosa after repeated administration of rebamipide. In addition, aspirin induced the increasing transport of fluorescine isothiocyanate-labeled dextrans with localized disruption and decreased expression of ZO-1 protein on rat gastric mucosal cell line RGM-1. Rebamipide effectively prevented aspirin-induced permeability changes and disruption of ZO-1 distribution. These results suggest that rebamipide protects against aspirin-induced gastric mucosal lesions by preserving gastric epithelial cell-to cell integrity in addition to the anti-inflammatory effects.

  20. Dietary l-threonine supplementation attenuates lipopolysaccharide-induced inflammatory responses and intestinal barrier damage of broiler chickens at an early age.

    Science.gov (United States)

    Chen, Yueping; Zhang, Hao; Cheng, Yefei; Li, Yue; Wen, Chao; Zhou, Yanmin

    2018-06-01

    This study was conducted to investigate the protective effects of l-threonine (l-Thr) supplementation on growth performance, inflammatory responses and intestinal barrier function of young broilers challenged with lipopolysaccharide (LPS). A total of 144 1-d-old male chicks were allocated to one of three treatments: non-challenged broilers fed a basal diet (control group), LPS-challenged broilers fed a basal diet without l-Thr supplementation and LPS-challenged broilers fed a basal diet supplemented with 3·0 g/kg l-Thr. LPS challenge was performed intraperitoneally at 17, 19 and 21 d of age, whereas the control group received physiological saline injection. Compared with the control group, LPS challenge impaired growth performance of broilers, and l-Thr administration reversed LPS-induced increase in feed/gain ratio. LPS challenge elevated blood cell counts related to inflammation, and pro-inflammatory cytokine concentrations in serum (IL-1β and TNF-α), spleen (IL-1β and TNF-α) and intestinal mucosa (jejunal interferon-γ (IFN-γ) and ileal IL-1β). The concentrations of intestinal cytokines in LPS-challenged broilers were reduced by l-Thr supplementation. LPS administration increased circulating d-lactic acid concentration, whereas it reduced villus height, the ratio between villus height and crypt depth and goblet density in both jejunum and ileum. LPS-induced decreases in jejunal villus height, intestinal villus height:crypt depth ratio and ileal goblet cell density were reversed with l-Thr supplementation. Similarly, LPS-induced alterations in the intestinal mRNA abundances of genes related to intestinal inflammation and barrier function (jejunal toll-like receptor 4, IFN- γ and claudin-3, and ileal IL-1 β and zonula occludens-1) were normalised with l-Thr administration. It can be concluded that l-Thr supplementation could attenuate LPS-induced inflammatory responses and intestinal barrier damage of young broilers.

  1. Structural Stability of Human Fibroblast Growth Factor-1 Is Essential for Protective Effects Against Radiation-Induced Intestinal Damage

    Energy Technology Data Exchange (ETDEWEB)

    Nakayama, Fumiaki, E-mail: f_naka@nirs.go.jp [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Umeda, Sachiko [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan); Yasuda, Takeshi [Department of Radiation Emergency Medicine, Research Center for Radiation Emergency Medicine, National Institute of Radiological Sciences, Chiba (Japan); Asada, Masahiro; Motomura, Kaori; Suzuki, Masashi [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Zakrzewska, Malgorzata [Faculty of Biotechnology, University of Wroclaw (Poland); Imamura, Toru [Signaling Molecules Research Laboratory, Biomedical Research Institute, National Institute of Advanced Industrial Science and Technology, Tsukuba, Ibaraki (Japan); Imai, Takashi [Advanced Radiation Biology Research Program, Research Center for Charged Particle Therapy, National Institute of Radiological Sciences, Chiba (Japan)

    2013-02-01

    Purpose: Human fibroblast growth factor-1 (FGF1) has radioprotective effects on the intestine, although its structural instability limits its potential for practical use. Several stable FGF1 mutants were created increasing stability in the order, wild-type FGF1, single mutants (Q40P, S47I, and H93G), Q40P/S47I, and Q40P/S47I/H93G. This study evaluated the contribution of the structural stability of FGF1 to its radioprotective effect. Methods and Materials: Each FGF1 mutant was administered intraperitoneally to BALB/c mice in the absence of heparin 24 h before or after total body irradiation (TBI) with {gamma}-rays at 8-12 Gy. Several radioprotective effects were examined in the jejunum. Results: Q40P/S47I/H93G could activate all subtypes of FGF receptors in vitro much more strongly than the wild-type without endogenous or exogenous heparin. Preirradiation treatment with Q40P/S47I/H93G significantly increased crypt survival more than wild-type FGF1 after TBI at 10 or 12 Gy, and postirradiation treatment with Q40P/S47I/H93G was effective in promoting crypt survival after TBI at 10, 11, or 12 Gy. In addition, crypt cell proliferation, crypt depth, and epithelial differentiation were significantly promoted by postirradiation treatment with Q40P/S47I/H93G. The level of stability of FGF1 mutants correlated with their mitogenic activities in vitro in the absence of heparin; however, preirradiation treatment with the mutants increased the crypt number to almost the same level as Q40P/S47I/H93G. When given 24 h after TBI at 10 Gy, all FGF1 mutants increased crypt survival more than wild-type FGF1, and Q40P/S47I/H93G had the strongest mitogenic effects in intestinal epithelial cells after radiation damage. Moreover, Q40P/S47I/H93G prolonged mouse survival after TBI because of the repair of intestinal damage. Conclusion: These findings suggest that the structural stability of FGF1 can contribute to the enhancement of protective effects against radiation-induced intestinal

  2. Intestinal Cancer

    Science.gov (United States)

    ... connects your stomach to your large intestine. Intestinal cancer is rare, but eating a high-fat diet ... increase your risk. Possible signs of small intestine cancer include Abdominal pain Weight loss for no reason ...

  3. Vascular lesions following radiation

    International Nuclear Information System (INIS)

    Fajardo, L.F.; Berthrong, M.

    1988-01-01

    The special radiation sensitivity of the vascular system is mainly linked to that of endothelial cells, which are perhaps the most radiation-vulnerable elements of mesenchymal tissues. Within the vascular tree, radiation injures most often capillaries, sinusoids, and small arteries, in that order. Lesions of veins are observed less often, but in certain tissues the veins are regularly damaged (e.g., intestine) or are the most affected structures (i.e., liver). Large arteries do suffer the least; however, when significant damage does occur in an elastic artery (e.g., thrombosis or rupture), it tends to be clinically significant and even fatal. Although not always demonstrable in human tissues, radiation vasculopathy generally is dose and time dependent. Like other radiation-induced lesions, the morphology in the vessels is not specific, but it is characteristic enough to be often recognizable. Vascular injury, especially by therapeutic radiation is not just a morphologic marker. It is a mediator of tissue damage; perhaps the most consistent pathogenetic mechanism in delayed radiation injury

  4. Influence of very short patch mismatch repair on SOS inducing lesions after aminoglycoside treatment in Escherichia coli.

    Science.gov (United States)

    Baharoglu, Zeynep; Mazel, Didier

    2014-01-01

    Low concentrations of aminoglycosides induce the SOS response in Vibrio cholerae but not in Escherichia coli. In order to determine whether a specific factor present in E. coli prevents this induction, we developed a genetic screen where only SOS inducing mutants are viable. We identified the vsr gene coding for the Vsr protein of the very short patch mismatch repair (VSPR) pathway. The effect of mismatch repair (MMR) mutants was also studied. We propose that lesions formed upon aminoglycoside treatment are preferentially repaired by VSPR without SOS induction in E. coli and by MMR when VSPR is impaired. Copyright © 2014 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

  5. Distinctive genomic signature of neural and intestinal organoids from familial Parkinson's disease patient-derived induced pluripotent stem cells.

    Science.gov (United States)

    Son, M-Y; Sim, H; Son, Y S; Jung, K B; Lee, M-O; Oh, J-H; Chung, S-K; Jung, C-R; Kim, J

    2017-12-01

    The leucine-rich repeat kinase 2 (LRRK2) G2019S mutation is the most common genetic cause of Parkinson's disease (PD). There is compelling evidence that PD is not only a brain disease but also a gastrointestinal disorder; nonetheless, its pathogenesis remains unclear. We aimed to develop human neural and intestinal tissue models of PD patients harbouring an LRRK2 mutation to understand the link between LRRK2 and PD pathology by investigating the gene expression signature. We generated PD patient-specific induced pluripotent stem cells (iPSCs) carrying an LRRK2 G2019S mutation (LK2GS) and then differentiated into three-dimensional (3D) human neuroectodermal spheres (hNESs) and human intestinal organoids (hIOs). To unravel the gene and signalling networks associated with LK2GS, we analysed differentially expressed genes in the microarray data by functional clustering, gene ontology (GO) and pathway analyses. The expression profiles of LK2GS were distinct from those of wild-type controls in hNESs and hIOs. The most represented GO biological process in hNESs and hIOs was synaptic transmission, specifically synaptic vesicle trafficking, some defects of which are known to be related to PD. The results were further validated in four independent PD-specific hNESs and hIOs by microarray and qRT-PCR analysis. We provide the first evidence that LK2GS also causes significant changes in gene expression in the intestinal cells. These hNES and hIO models from the same genetic background of PD patients could be invaluable resources for understanding PD pathophysiology and for advancing the complexity of in vitro models with 3D expandable organoids. © 2017 British Neuropathological Society.

  6. Increased intestinal mucosal turnover and radiosensitivity to supralethal whole-body irradiation resulting from cholic acid-induced alterations of the intestinal microecology of germfree CFW mice

    International Nuclear Information System (INIS)

    Mastromarino, A.J.; Wilson, R.

    1976-01-01

    The prolonged mean survival time of germfree mice, compared to conventional mice, after exposure to 1000-10,000 rad whole-body irradiation has been postulated to be a function of an increased turnover time of the intestinal mucosal cells caused by the absence of free bile acids. To test this hypothesis, the diet of germ-free CFW mice was supplemented with 0.15 percent cholic acid for 2 weeks. The turnover of thymidine-labeled intestinal mucosal cells and the radiosensitivity to supralethal whole-body irradiation were significantly increased compared to germfree controls. There was a positive correlation between increased survivial time after supralethal whole-body irradiation and slower intestinal mucosal turnover time. Germfree mice supplemented with cholic acid had intestinal mucosal turnover times comparable to those of conventionalized controls. Although cholic acid reduces the mean survival time of germfree mice after suppralethal whole-body irradiation, the mean survival value is significantly greater than the conventionalized controls. Supplementing the diet of conventionalized CFW mice with cholic acid did not significantly decrease the intestinal mucosal turnover time nor did it significantly alter their radiosensitivity to supralethal whole-body irradiation. The data suggest that cholic acid is one of the microecological factors responsible for controlling the mucosal renewal rate and the mean survival time after whole-body irradiation

  7. Gastroprotective effect of diligustilide isolated from roots of Ligusticum porteri coulter & rose (Apiaceae) on ethanol-induced lesions in rats.

    Science.gov (United States)

    Velázquez-Moyado, Josué A; Martínez-González, Alejandro; Linares, Edelmira; Bye, Robert; Mata, Rachel; Navarrete, Andrés

    2015-11-04

    The rhizome of Ligusticum porteri Coulter& Rose (LP) has been traditionally used by the ethnic group Raramuri in the North of México for treatment of diabetes, tuberculosis, stomachaches, diarrhea and ritual healing ceremonies. It is use as antiulcer remedy has been extended to all Mexico. To evaluate the gastroprotective activity of LP organic extracts and the major natural product diligustilide (DLG),using as experimental model the inhibition of the ethanol-induced lesions in rats. Gastric ulcers were induced by intragastric instillation of absolute ethanol (1 mL). We tested the gastroprotective activity of the organic extracts of LP and the pure compound DLG. The ulcer index (UI) was determined to measure the activity. In order to elucidate the action mechanism of DLG the animals were treated with L-NAME, N-ethylmalemide, Forskolin, 2',5'-dideoxyadenosine, Indomethacin, Glibenclameide, Diazoxide, NaHS and DL-Propargylglycine. The pylorus-ligated rat model was used to measure gastric secretion. The oral administration of organic extracts of Ligusticum porteri showed gastroprotective effect at 30 mg/Kg on ethanol induced gastric lesions; hexane and dichloromethane extracts were the most active. DLG was the major compound in the hexane extract. This compound at 10 mg/kg prevented significantly the gastric injuries induced by ethanol. The alkylation of endogenous non-protein-SH groups with N-ethylmaleimide abolished the gastroprotective effect of DLG and blocking the formation of endogenous prostaglandins by the pretreatment with indomethacin attenuated the gastroprotective effect of DLG. The gastroprotective activity demonstrated in this study tends to support the ethnomedical use of Ligusticum porteri roots. DLG, isolated as major compound of this medicinal plant has a clear gastroprotective effect on the ethanol-induced gastric lesions. The results suggest that the antiulcer activity of DLG depends on the participation of the endogenous non-protein -SH groups

  8. Evidence for a role of orexin/hypocretin system in vestibular lesion-induced locomotor abnormalities in rats

    Directory of Open Access Journals (Sweden)

    Leilei Pan

    2016-07-01

    Full Text Available Vestibular damage can induce locomotor abnormalities in both animals and humans. Rodents with bilateral vestibular loss showed vestibular deficits syndrome such as circling, opisthotonus as well as locomotor and exploratory hyperactivity. Previous studies have investigated the changes in the dopamine system after vestibular loss, but the results are inconsistent and inconclusive. Numerous evidences indicate that the orexin system is implicated in central motor control. We hypothesized that orexin may be potentially involved in vestibular loss-induced motor disorders. In this study, we examined the effects of arsanilate- or 3, 3′-iminodipropionitrile (IDPN-induced vestibular lesion (AVL or IVL on the orexin-A (OXA labeling in rat hypothalamus using immunohistochemistry. The vestibular lesion-induced locomotor abnormalities were recorded and verified using a histamine H4 receptor antagonist JNJ7777120 (20 mg/kg, i.p.. The effects of the orexin receptor type 1 antagonist SB334867 (16 μg, i.c.v. on these behavior responses were also investigated. At 72 h post-AVL and IVL, animals exhibited vestibular deficit syndrome and locomotor hyperactivity in the home cages. These responses were significantly alleviated by JNJ7777120 which also eliminated AVL-induced increases in exploratory behavior in an open field. The numbers of OXA-labeled neurons in the hypothalamus were significantly increased in the AVL animals at 72 h post-AVL and in the IVL animals at 24, 48 and 72 h post-IVL. SB334867 significantly attenuated the vestibular deficit syndrome and locomotor hyperactivity at 72 h post-AVL and IVL. It also decreased exploratory behavior in the AVL animals. These results suggested that the alteration of OXA expression might contribute to locomotor abnormalities after acute vestibular lesion. The orexin receptors might be the potential therapeutic targets for vestibular disorders.

  9. Treatment of rape-induced urogenital and lower gastrointestinal lesions among girls aged 5 years or younger.

    Science.gov (United States)

    Mukwege, Denis; Alumeti, Desiré; Himpens, Jacques; Cadière, Guy-Bernard

    2016-03-01

    To evaluate outcomes after treatment of rape-induced urogenital and lower gastrointestinal lesions among young girls. In a retrospective study, data were assessed from girls aged 5 years or younger who were treated for sexual-assault-related injuries at the General Referral Hospital, Panzi, Bukavu, Democratic Republic of Congo, between 2004 and 2014. Data were obtained from review of charts, records of the mother's impressions and physical examinations, and photographic evidence. Elective surgery had been reserved for patients experiencing fecal and/or urinary incontinence. Overall, 205 girls aged 5 years or younger presented with rape injuries: 162 (79.1%) had only mucocutaneous lesions, 22 (10.7%) had musculocutaneous lesions, and 21 (10.2%) had musculocutaneous lesions complicated by fecal and/or urinary incontinence. Among the 21 girls who underwent perineal surgery, two with fecal and urinary incontinence and perforation of the peritoneum of Douglas pouch were additionally treated by laparoscopy. Among 16 patients with fecal incontinence, the continence score had improved significantly at 10.4 months after surgery (Prape survivors aged 5 years or younger, a treatment strategy by which surgery is reserved for incontinent patients provided good cosmetic and functional outcomes. Copyright © 2015 International Federation of Gynecology and Obstetrics. Published by Elsevier Ireland Ltd. All rights reserved.

  10. Selective brain lesions reduce morphine- and radiation-induced locomotor hyperactivity of the C57BL/6J mouse

    International Nuclear Information System (INIS)

    Mickley, G.A.; Stevens, K.E.; White, G.A.; Gibbs, G.L.

    1984-01-01

    The apparent resemblance between the stereotypic locomotor hyperactivity observed after either an injection of morphine or irradiation of the C57BL/6J mouse has suggested the possibility of similar biochemical and neuroanatomical substrates of these behaviors. In this study the authors made selective brain lesions in an attempt to reverse the locomotor response observed after morphine (30 mg/kg) or radiation (1500 rads /sup 60/Co) treatments. Lesions impinging on both the dorso-medial caudate and lateral septal nuclei caused a significant decrease in morphine-induced and radiogenic locomotion. Lesions of the individual brain areas did not significantly alter the opiate locomotor response. This reduction in locomotion could not be attributed to a generalized post-surgical lethargy since other brain lesions of similar size did not significantly suppress these behaviors. These data suggest the possibility of some common central nervous system mechanisms which may support the stereotypic locomotor hyperactivity observed in the C57BL/6J mouse after either morphine or radiation treatment

  11. Synthesis of modified oligonucleotides that contain purine and pyrimidine radio-induced base lesions

    International Nuclear Information System (INIS)

    Romieu, Anthony

    1999-01-01

    Different factors as oxidizing or carcinogenesis agents, UV and ionizing radiations,.... can generate a wide, spectrum of DNA base damages. In order to study the biochemical and structural features of these DNA damages, it is important to prepare short DNA fragments (20 to 50 bases long) bearing a single or several modifications at specific sites in their sequences. The chemical synthesis is a powerful tool to prepare such modified DNA fragments. This work focusses on the chemical incorporation of several modified nucleosides formed in DNA by ionizing radiations or by photo-sensitization. The first part of this study describes the preparation of a phosphoramidite synthon of 5-hydroxy-2'-deoxyuridine and its subsequent incorporation into synthetic oligonucleotides ranging from 14 to 33 bases long. In a second part (chapters Ill and IV), the synthesis and incorporation of original radiation-induced tandem lesions: the carbon-bridged cyclo-nucleosides are presented. Both (5'R)- and (5'S) diastereomers of 5',8-cyclo-2'-deoxyadenosine and 5',8-cyclo-2'-deoxyguanosine have been individually inserted into various different oligonucleotides (3 to 22 bases long) by using the standard phosphoramidite chemistry. The chemical incorporation of a pyrimidine analogue: (5'S, 6S)-5',6-cyclo-5,6-dihydro-thymidine has been also achieved. The loss of aromaticity of this modified nucleoside and its poor reactivity required the development of a synthetic strategy entirely different from that used for the preparation and subsequent incorporation of the phosphoramidite synthons of 5',8-cyclo-purine-2'-deoxyribo-nucleosides. The third part of this study deals with the synthesis of a phosphoramidite synthon of 4-hydroxy-8-oxo-4,8-dihydro-2'-deoxyguanosine. The two (4R)- and (4S)- diastereomers of this oxidized purine have been separated and individually inserted in several synthetic DNA fragments. No epimerization of C-4 position was observed during the solid-phase synthesis and during the

  12. Gamma radiation-induced conditioned taste aversions in rats: A comparison of the protective effects of area postrema lesions with differing doses of radiation

    International Nuclear Information System (INIS)

    Ossenkopp, K.P.; Giugno, L.

    1989-01-01

    Lesions which destroy the area postrema (AP) and damage the adjacent nucleus of the solitary tract (NTS) attenuate or abolish conditioned taste aversions (CTA) induced by a variety of pharmacological agents as well as exposure to radiation. In the present experiment, 4 groups of male rats received lesions of AP and 4 groups were given sham lesions. One sham-lesioned and one AP-lesioned group were given a single pairing of 1-hr access to a novel 0.10% sodium saccharin solution followed immediately with exposure to 0, 100, 200, or 400 rad of gamma radiation, respectively. Four days later all groups were given daily two-bottle preference tests (saccharin vs. water) on 4 consecutive days. The sham-lesioned groups exposed to the radiation (100, 200, or 400 rad) developed profound aversions to the saccharin on all test days (p less than 0.001). In contrast, all of the AP-lesioned groups as well as the sham-irradiated (0 rad) sham-lesioned group exhibited strong, comparable (p greater than 0.30) preferences for saccharin. Thus, lesion of AP abolished the radiation-induced CTA at all dose levels of radiation. These results raise the possibility of pharmacological intervention at the level of AP to prevent radiation-induced CTA in cancer patients undergoing radiation therapy

  13. Use of 2-octyl cyanoacrylate adhesive in rat liver induced lesion.

    Science.gov (United States)

    Santos, Orlando José dos; Marques, Giancarlo de Souza; Sauaia Filho, Euler Nicolau; Frota, Gustavo Medeiros; Santos, Rayan Haquim Pinheiro; Santos, Rennan Abud Pinheiro

    2012-09-01

    To evaluate the healing process of rat traumatic liver lesion corrected with the use of 2-octyl cyanoacrylate adhesive, compared to the use of biologically absorbable chromed catgut thread suture. Thirty mail adult rats were divided into two groups (15 per group) according to the used method for liver lesion correction as follows: adhesive group (AG), and catgut group (CG); each group being divided into three subsets of five animals (7th, 14th, and 21st day), respectively, according to post-surgery evaluation. All animals were submitted to homogeneous lesion applying synthetic bonding to AG and using chromed catgut suture to CG for lesion correction. Macroscopic and microscopic parameters of healing processes were evaluated. Both groups of animals showed excellent abdominal wall healing, with no evidence of infection, and no abdominal cavity peritonitis or abscess. The presence of adherence was observed in both groups with no statistically significant difference. As to macroscopic evaluation, there was statistically significant difference with respect to specific factors of clinical inflammation (ischemic inflammation and giant celular inflammatory reaction) between animals evaluated on the 10th day (ischemic necrosis and giant cellular inflammatory reaction) among animals evaluated on the 14th day (A14 versus C14). Applying 2-octyl-cyanoacrylate adhesive for correcting rat liver lesion does not change healing process when compared to the use of chromed catgut stitch.

  14. Protective effect of Bifidobacterium infantis CGMCC313-2 on ovalbumin-induced airway asthma and β-lactoglobulin-induced intestinal food allergy mouse models

    Science.gov (United States)

    Liu, Meng-Yun; Yang, Zhen-Yu; Dai, Wen-Kui; Huang, Jian-Qiong; Li, Yin-Hu; Zhang, Juan; Qiu, Chuang-Zhao; Wei, Chun; Zhou, Qian; Sun, Xin; Feng, Xin; Li, Dong-Fang; Wang, He-Ping; Zheng, Yue-Jie

    2017-01-01

    AIM To determine whether oral administration of Bifidobacterium infantis CGMCC313-2 (B. infantis CGMCC313-2) inhibits allergen-induced airway inflammation and food allergies in a mouse model. METHODS Ovalbumin (OVA)-induced allergic asthma and β-lactoglobulin-induced food allergy mouse models were used in this study. Following oral administration of B. infantis CGMCC313-2 during or after allergen sensitization, histopathologic changes in the lung and intestine were evaluated by hematoxylin and eosin (HE) staining. In the allergic asthma mouse model, we evaluated the proportion of lung-infiltrating inflammatory cells. OVA-specific IgE and IgG1 levels in serum and cytokine levels in bronchoalveolar lavage fluid (BALF) were also assessed. In the food allergy mouse model, the levels of total IgE and cytokines in serum were measured. RESULTS Oral administration of B. infantis CGMCC313-2 during or after allergen sensitization suppressed allergic inflammation in lung and intestinal tissues, while the proportion of infiltrating inflammatory cells was significantly decreased in the BALF of allergic asthma mice. Moreover, B. infantis CGMCC313-2 decreased the serum levels of total IgE in food allergy mice, and reductions in IgE and IgG1 were also observed in OVA-induced allergic asthma mice. The expression of interleukin-4 (IL-4) and IL-13 in both serum and BALF was suppressed following the administration of B. infantis CGMCC313-2, while an effect on serum IL-10 levels was not observed. CONCLUSION B. infantis CGMCC313-2 inhibits the secretion of allergen-induced IgE, IL-4 and IL-13, and attenuates allergic inflammation. PMID:28405142

  15. Effect of acyclovir on radiation- and chemotherapy-induced mouth lesions

    International Nuclear Information System (INIS)

    Bubley, G.J.; Chapman, B.; Chapman, S.K.; Crumpacker, C.S.; Schnipper, L.E.

    1989-01-01

    Several chemotherapeutic regimens and radiation therapy, if delivered to the oral mucosa, are associated with a high frequency of mouth lesions. The cause of this side effect is not known for certain, but in past studies it has sometimes been associated with the ability to culture herpes simplex virus type 1 from the mouth. In a double-blind prospective trial, patients with head and neck tumors treated with chemotherapy or radiation therapy were treated with either acyclovir or placebo. Although the frequency of culture-positive herpes simplex virus was low in the untreated group, it was significantly lower, zero, in the acyclovir-treated group. However, there were no differences in the frequency or type of mouth lesions experienced by patients receiving either radiation or chemotherapy who were taking acyclovir or placebo. These results suggest that herpes simplex virus is not a frequent cause or complication of oral lesions afflicting this patient population

  16. Perforant path lesioning induces sprouting of CA3-associated fibre systems in mouse hippocampal formation

    DEFF Research Database (Denmark)

    Drøjdahl, Nina; Hegelund, Iørn V; Poulsen, Frantz R

    2002-01-01

    mice. We found that lesioning led to translaminar sprouting of Timm stained regio inferior hippocampus (CA3)-associated fibre systems into the denervated termination zones of the CA3 and dentate gyrus, from the adjacent non-denervated stratum radiatum of CA3. Differences were seen in the Timm staining...... pattern of the two strains of mice, while the response to lesioning appeared similar albeit less pronounced than that observed in the rat. We also observed an intensified acetylcholine esterase staining reflective of cholinergic sprouting in the denervated perforant path termination zones, which...... was particularly prominent in areas with sprouting of Timm stained CA3-associated fibres. Finally, we showed that some of the sprouting fibres within the CA3 were myelinated, due to an increased density of silver impregnated myelinated fibres in this region after lesioning. These results show that the basic...

  17. Lesion-induced DNA weak structural changes detected by pulsed EPR spectroscopy combined with site-directed spin labelling.

    Science.gov (United States)

    Sicoli, Giuseppe; Mathis, Gérald; Aci-Sèche, Samia; Saint-Pierre, Christine; Boulard, Yves; Gasparutto, Didier; Gambarelli, Serge

    2009-06-01

    Double electron-electron resonance (DEER) was applied to determine nanometre spin-spin distances on DNA duplexes that contain selected structural alterations. The present approach to evaluate the structural features of DNA damages is thus related to the interspin distance changes, as well as to the flexibility of the overall structure deduced from the distance distribution. A set of site-directed nitroxide-labelled double-stranded DNA fragments containing defined lesions, namely an 8-oxoguanine, an abasic site or abasic site analogues, a nick, a gap and a bulge structure were prepared and then analysed by the DEER spectroscopic technique. New insights into the application of 4-pulse DEER sequence are also provided, in particular with respect to the spin probes' positions and the rigidity of selected systems. The lesion-induced conformational changes observed, which were supported by molecular dynamics studies, confirm the results obtained by other, more conventional, spectroscopic techniques. Thus, the experimental approaches described herein provide an efficient method for probing lesion-induced structural changes of nucleic acids.

  18. Smoking cessation induces profound changes in the composition of the intestinal microbiota in humans.

    Directory of Open Access Journals (Sweden)

    Luc Biedermann

    Full Text Available BACKGROUND: The human intestinal microbiota is a crucial factor in the pathogenesis of various diseases, such as metabolic syndrome or inflammatory bowel disease (IBD. Yet, knowledge about the role of environmental factors such as smoking (which is known to influence theses aforementioned disease states on the complex microbial composition is sparse. We aimed to investigate the role of smoking cessation on intestinal microbial composition in 10 healthy smoking subjects undergoing controlled smoking cessation. METHODS: During the observational period of 9 weeks repetitive stool samples were collected. Based on abundance of 16S rRNA genes bacterial composition was analysed and compared to 10 control subjects (5 continuing smokers and 5 non-smokers by means of Terminal Restriction Fragment Length Polymorphism analysis and high-throughput sequencing. RESULTS: Profound shifts in the microbial composition after smoking cessation were observed with an increase of Firmicutes and Actinobacteria and a lower proportion of Bacteroidetes and Proteobacteria on the phylum level. In addition, after smoking cessation there was an increase in microbial diversity. CONCLUSIONS: These results indicate that smoking is an environmental factor modulating the composition of human gut microbiota. The observed changes after smoking cessation revealed to be similar to the previously reported differences in obese compared to lean humans and mice respectively, suggesting a potential pathogenetic link between weight gain and smoking cessation. In addition they give rise to a potential association of smoking status and the course of IBD.

  19. Unilateral Lesion of Dopamine Neurons Induces Grooming Asymmetry in the Mouse.

    Science.gov (United States)

    Pelosi, Assunta; Girault, Jean-Antoine; Hervé, Denis

    2015-01-01

    Grooming behaviour is the most common innate behaviour in animals. In rodents, it consists of sequences of movements organized in four phases, executed symmetrically on both sides of the animal and creating a syntactic chain of behavioural events. The grooming syntax can be altered by stress and novelty, as well as by several mutations and brain lesions. Grooming behaviour is known to be affected by alterations of the dopamine system, including dopamine receptor modulation, dopamine alteration in genetically modified animals, and after brain lesion. While a lot is known about the initiation and syntactic modifications of this refined sequence of movements, effects of unilateral lesion of dopamine neurons are unclear particularly regarding the symmetry of syntactic chains. In the present work we studied grooming in mice unilaterally lesioned in the medial forebrain bundle by 6-hydroxydopamine. We found a reduction in completion of grooming bouts, associated with reduction in number of transitions between grooming phases. The data also revealed the development of asymmetry in grooming behaviour, with reduced tendency to groom the contralateral side to the lesion. Symmetry was recovered following treatment with L-DOPA. Thus, the present work shows that unilateral lesion of dopamine neurons reduces self-grooming behaviour by affecting duration and numbers of events. It produces premature discontinuation of grooming chains but the sequence syntax remains correct. This deficient grooming could be considered as an intrinsic symptom of Parkinson's disease in animal models and could present some similarities with abnormalities of motor movement sequencing seen in patients. Our study also suggests grooming analysis as an additional method to screen parkinsonism in animal models.

  20. Histopathologic changes induced in rats by localized x-irradiation of an exteriorized segment of the small intestine

    Energy Technology Data Exchange (ETDEWEB)

    Sebes, J I; Zaldivar, R; Vogel, Jr, H H [Tennessee Univ., Memphis (USA). Dept. of Radiation Oncology; Tennessee Univ., Memphis (USA). Dept. of Diagnostic Radiology)

    1975-10-01

    The sequence of histopathological changes was described after X-irradiation of the exteriorized segment (3 cm) of the rat ileum with a single dose of 2,200 R. A one-year follow-up was provided in rats whose exteriorized intestinal segments were irradiated. Comparisons were made between one group of animals in which the superior mesenteric artery and vein were clamped during irradiation and a second group in which these vessels were not clamped. A third group of sham-irradiated controls was used for comparisons. There was a delay in the onset and progression of the radiation damage to the mucosa of the hypoxic animals in the acute post-irradiation phase. In addition, prolongation of survival in the rats with the superior mesenteric vessels clamped was observed. Mucosal regeneration was noted, occurring at 52 days post-exposure. No adenocarcinomas were found up to 354 days after irradiation. An angiofibroma and a highly differentiated osteoid lesion were described.

  1. Bisphosphonate-Induced Osteonecrosis of the Maxilla Resembling a Persistent Endodontic Lesion.

    Science.gov (United States)

    Mosaferi, Hossein; Fazlyab, Mahta; Sharifi, Sanaz; Rahimian, Sepideh

    2016-01-01

    A 52-year-old Caucasian woman suffering from pain in the anterior maxillary region, presented to the clinic. Examination revealed a draining sinus tract in the buccal vestibule of the maxilla in the left anterior segment and expansion in the middle of palate. On conventional radiographic examination the lesion was initially assumed to be a periapical problem related to the incisors but subsequently it was diagnosed to be a bisphosphonate osteonecrosis. Acquiring a comprehensive medical history from the patients, conducting the clinical vitality tests and most importantly being familiar with the non-odontogenic lesions that can be side effects of specific medications are important requirements for reaching a correct diagnosis.

  2. Radiation-induced focal cortical necrosis of the femur presenting as a lytic lesion

    Energy Technology Data Exchange (ETDEWEB)

    Ilaslan, Hakan; Schils, Jean [Cleveland Clinic, Musculoskeletal Radiology, Cleveland, OH (United States); Joyce, Michael [Cleveland Clinic, Orthopedic Oncology, Cleveland, OH (United States); Shah, Chirag [Cleveland Clinic, Radiation Oncology, Cleveland, OH (United States); Zhang, Yaxia [Cleveland Clinic, Pathology, Cleveland, OH (United States)

    2017-11-15

    Management of soft tissue sarcomas is often complicated, requiring radiation before and in some cases after limb-sparing surgery. Radiation necrosis is a severe complication after radiation treatment and is typically dose related and involves medullary bone. We report on two cases of hitherto unreported focal circumscribed intra-cortical lytic lesions within the radiation portal, which appeared 19 months and 31 months, respectively, after the conclusion of radiation treatment. Both patients had a history of soft tissue sarcoma treated with radiation (66 Gy) and surgical resection. Biopsy of these lesions showed necrotic bone attributed to radiation. (orig.)

  3. Intestinal barrier dysfunction develops at the onset of experimental autoimmune encephalomyelitis, and can be induced by adoptive transfer of auto-reactive T cells.

    Directory of Open Access Journals (Sweden)

    Mehrnaz Nouri

    Full Text Available Multiple sclerosis (MS is a chronic inflammatory demyelinating disease of the central nervous system with a pathogenesis involving a dysfunctional blood-brain barrier and myelin-specific, autoreactive T cells. Although the commensal microbiota seems to affect its pathogenesis, regulation of the interactions between luminal antigens and mucosal immune elements remains unclear. Herein, we investigated whether the intestinal mucosal barrier is also targeted in this disease. Experimental autoimmune encephalomyelitis (EAE, the prototypic animal model of MS, was induced either by active immunization or by adoptive transfer of autoreactive T cells isolated from these mice. We show increased intestinal permeability, overexpression of the tight junction protein zonulin and alterations in intestinal morphology (increased crypt depth and thickness of the submucosa and muscularis layers. These intestinal manifestations were seen at 7 days (i.e., preceding the onset of neurological symptoms and at 14 days (i.e., at the stage of paralysis after immunization. We also demonstrate an increased infiltration of proinflammatory Th1/Th17 cells and a reduced regulatory T cell number in the gut lamina propria, Peyer's patches and mesenteric lymph nodes. Adoptive transfer to healthy mice of encephalitogenic T cells, isolated from EAE-diseased animals, led to intestinal changes similar to those resulting from the immunization procedure. Our findings show that disruption of intestinal homeostasis is an early and immune-mediated event in EAE. We propose that this intestinal dysfunction may act to support disease progression, and thus represent a potential therapeutic target in MS. In particular, an increased understanding of the regulation of tight junctions at the blood-brain barrier and in the intestinal wall may be crucial for design of future innovative therapies.

  4. Intestinal Barrier Dysfunction Develops at the Onset of Experimental Autoimmune Encephalomyelitis, and Can Be Induced by Adoptive Transfer of Auto-Reactive T Cells

    Science.gov (United States)

    Nouri, Mehrnaz; Bredberg, Anders; Weström, Björn; Lavasani, Shahram

    2014-01-01

    Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system with a pathogenesis involving a dysfunctional blood-brain barrier and myelin-specific, autoreactive T cells. Although the commensal microbiota seems to affect its pathogenesis, regulation of the interactions between luminal antigens and mucosal immune elements remains unclear. Herein, we investigated whether the intestinal mucosal barrier is also targeted in this disease. Experimental autoimmune encephalomyelitis (EAE), the prototypic animal model of MS, was induced either by active immunization or by adoptive transfer of autoreactive T cells isolated from these mice. We show increased intestinal permeability, overexpression of the tight junction protein zonulin and alterations in intestinal morphology (increased crypt depth and thickness of the submucosa and muscularis layers). These intestinal manifestations were seen at 7 days (i.e., preceding the onset of neurological symptoms) and at 14 days (i.e., at the stage of paralysis) after immunization. We also demonstrate an increased infiltration of proinflammatory Th1/Th17 cells and a reduced regulatory T cell number in the gut lamina propria, Peyer's patches and mesenteric lymph nodes. Adoptive transfer to healthy mice of encephalitogenic T cells, isolated from EAE-diseased animals, led to intestinal changes similar to those resulting from the immunization procedure. Our findings show that disruption of intestinal homeostasis is an early and immune-mediated event in EAE. We propose that this intestinal dysfunction may act to support disease progression, and thus represent a potential therapeutic target in MS. In particular, an increased understanding of the regulation of tight junctions at the blood-brain barrier and in the intestinal wall may be crucial for design of future innovative therapies. PMID:25184418

  5. Cyclical DNA Methylation and Histone Changes Are Induced by LPS to Activate COX-2 in Human Intestinal Epithelial Cells.

    Directory of Open Access Journals (Sweden)

    Tiziana Angrisano

    Full Text Available Bacterial lipopolysaccharide (LPS induces release of inflammatory mediators both in immune and epithelial cells. We investigated whether changes of epigenetic marks, including selected histone modification and DNA methylation, may drive or accompany the activation of COX-2 gene in HT-29 human intestinal epithelial cells upon exposure to LPS. Here we describe cyclical histone acetylation (H3, methylation (H3K4, H3K9, H3K27 and DNA methylation changes occurring at COX-2 gene promoter overtime after LPS stimulation. Histone K27 methylation changes are carried out by the H3 demethylase JMJD3 and are essential for COX-2 induction by LPS. The changes of the histone code are associated with cyclical methylation signatures at the promoter and gene body of COX-2 gene.

  6. Grapefruit-seed extract attenuates ethanol-and stress-induced gastric lesions via activation of prostaglandin, nitric oxide and sensory nerve pathways

    OpenAIRE

    Brzozowski, Tomasz; Konturek, Peter C; Drozdowicz, Danuta; Konturek, Stanislaw J; Zayachivska, Oxana; Pajdo, Robert; Kwiecien, Slawomir; Pawlik, Wieslaw W; Hahn, Eckhart G

    2005-01-01

    AIM: Grapefruit-seed extract (GSE) containing flavonoids, possesses antibacterial and antioxidative properties but whether it influences the gastric defense mechanism and gastroprotection against ethanol- and stress-induced gastric lesions remains unknown.

  7. Molecular - and genetic aspects of the repair of the lesions induced by the furocoumarin photoaddition in Sacharomyces cerevisiae : role of the PSO genes

    International Nuclear Information System (INIS)

    Henriques, J.A.P.

    1982-01-01

    Experiences with strains of Sacharomyces cerevisiae with the aim to obtain informations about molecular steps and genetic control of the DNA photo-induced lesion repair by furocoumarins are described. (M.A.) [pt

  8. Dietary Bacillus subtilis-based direct-fed microbials alleviate LPS-induced intestinal immunological stress and improve intestinal barrier gene expression in commercial broiler chickens

    Science.gov (United States)

    The present study investigated the effects of B. subtilis-based probiotics on performance, modulation of host inflammatory responses and intestinal barrier integrity of broilers subjected to LPS challenge. Birds at day 0 of age were randomly allocated to one of the 3 dietary treatments - controls, ...

  9. Modulation of Intestinal Barrier and Bacterial Endotoxin Production Contributes to the Beneficial Effect of Nicotinic Acid on Alcohol-Induced Endotoxemia and Hepatic Inflammation in Rats

    Directory of Open Access Journals (Sweden)

    Wei Zhong

    2015-10-01

    Full Text Available Alcohol consumption causes nicotinic acid deficiency. The present study was undertaken to determine whether dietary nicotinic acid supplementation provides beneficial effects on alcohol-induced endotoxin signaling and the possible mechanisms at the gut-liver axis. Male Sprague-Dawley rats were pair-fed the Lieber-DeCarli liquid diets containing ethanol or isocaloric maltose dextrin for eight weeks, with or without dietary supplementation with 750 mg/liter nicotinic acid. Chronic alcohol feeding elevated the plasma endotoxin level and activated hepatic endotoxin signaling cascade, which were attenuated by nicotinic acid supplementation. Alcohol consumption remarkably decreased the mRNA levels of claudin-1, claudin-5, and ZO-1 in the distal intestine, whereas nicotinic acid significantly up-regulated these genes. The concentrations of endotoxin, ethanol, and acetaldehyde in the intestinal contents were increased by alcohol exposure, and niacin supplementation reduced the intestinal endotoxin and acetaldehyde levels. Nicotinic acid supplementation upregulated the intestinal genes involved in aldehyde detoxification via transcriptional regulation. These results demonstrate that modulation of the intestinal barrier function and bacterial endotoxin production accounts for the inhibitory effects of nicotinic acid on alcohol-induced endotoxemia and hepatic inflammation.

  10. Activation-Induced TIM-4 Expression Identifies Differential Responsiveness of Intestinal CD103+ CD11b+ Dendritic Cells to a Mucosal Adjuvant.

    Directory of Open Access Journals (Sweden)

    Kerry L Hilligan

    Full Text Available Macrophage and dendritic cell (DC populations residing in the intestinal lamina propria (LP are highly heterogeneous and have disparate yet collaborative roles in the promotion of adaptive immune responses towards intestinal antigen. Under steady-state conditions, macrophages are efficient at acquiring antigen but are non-migratory. In comparison, intestinal DC are inefficient at antigen uptake but migrate to the mesenteric lymph nodes (mLN where they present antigen to T cells. Whether such distinction in the roles of DC and macrophages in the uptake and transport of antigen is maintained under immunostimulatory conditions is less clear. Here we show that the scavenger and phosphatidylserine receptor T cell Immunoglobulin and Mucin (TIM-4 is expressed by the majority of LP macrophages at steady-state, whereas DC are TIM-4 negative. Oral treatment with the mucosal adjuvant cholera toxin (CT induces expression of TIM-4 on a proportion of CD103+ CD11b+ DC in the LP. TIM-4+ DC selectively express high levels of co-stimulatory molecules after CT treatment and are detected in the mLN a short time after appearing in the LP. Importantly, intestinal macrophages and DC expressing TIM-4 are more efficient than their TIM-4 negative counterparts at taking up apoptotic cells and soluble antigen ex vivo. Taken together, our results show that CT induces phenotypic changes to migratory intestinal DC that may impact their ability to take up local antigens and in turn promote the priming of mucosal immunity.

  11. Alpha-Melanocyte Stimulating Hormone Protects against Cytokine-Induced Barrier Damage in Caco-2 Intestinal Epithelial Monolayers.

    Directory of Open Access Journals (Sweden)

    Judit Váradi

    Full Text Available Alpha-melanocyte-stimulating hormone (α-MSH is a potent anti-inflammatory peptide with cytoprotective effect in various tissues. The present investigation demonstrates the ability of α-MSH to interact with intestinal epithelial cell monolayers and mitigate inflammatory processes of the epithelial barrier. The protective effect of α-MSH was studied on Caco-2 human intestinal epithelial monolayers, which were disrupted by exposure to tumor necrosis factor-α and interleukin-1β. The barrier integrity was assessed by measuring transepithelial electric resistance (TEER and permeability for marker molecules. Caco-2 monolayers were evaluated by immunohistochemistry for expression of melanocortin-1 receptor and tight junction proteins ZO-1 and claudin-4. The activation of nuclear factor kappa beta (NF-κB was detected by fluorescence microscopy and inflammatory cytokine expression was assessed by flow cytometric bead array cytokine assay. Exposure of Caco-2 monolayers to proinflammatory cytokines lowered TEER and increased permeability for fluorescein and albumin, which was accompanied by changes in ZO-1 and claudin-4 immunostaining. α-MSH was able to prevent inflammation-associated decrease of TEER in a dose-dependent manner and reduce the increased permeability for paracellular marker fluorescein. Further immunohistochemistry analysis revealed proinflammatory cytokine induced translocation of the NF-κB p65 subunit into Caco-2 cell nuclei, which was inhibited by α-MSH. As a result the IL-6 and IL-8 production of Caco-2 monolayers were also decreased with different patterns by the addition of α-MSH to the culture medium. In conclusion, Caco-2 cells showed a positive immunostaining for melanocortin-1 receptor and α-MSH protected Caco-2 cells against inflammatory barrier dysfunction and inflammatory activation induced by tumor necrosis factor-α and interleukin-1β cytokines.

  12. Identification and Map-Based Cloning of the Light-Induced Lesion Mimic Mutant 1 (LIL1) Gene in Rice.

    Science.gov (United States)

    Zhou, Qian; Zhang, Zhifei; Liu, Tiantian; Gao, Bida; Xiong, Xingyao

    2017-01-01

    The hypersensitive response (HR) is a mechanism by which plants prevent the spread of pathogen. Despite extensive study, the molecular mechanisms underlying HR remain poorly understood. Lesion mimic mutants (LMMs), such as LIL1 that was identified in an ethylmethane sulfonate mutagenized population of Indica rice ( Oryza sativa L. ssp. Indica ) 93-11, can be used to study the HR. Under natural field conditions, the leaves of LIL1 mutant plants exhibited light-induced, small, rust-red lesions that first appeared at the leaf tips and subsequently expanded throughout the entire leaf blade to the leaf sheath. Histochemical staining indicated that LIL1 lesions displayed an abnormal accumulation of reactive oxygen species (ROS) and resulted from programmed cell death (PCD). The LIL1 mutants also displayed increased expression of defense-related genes and enhanced resistance to rice blast fungus ( Magnaporthe grisea ). Genetic analysis showed that mutation of LIL1 created a semi-dominant allele. Using 1,758 individuals in the F 2 population, LIL1 was mapped in a 222.3 kb region on the long arm of chromosome 7. That contains 12 predicted open reading frames (ORFs). Sequence analysis of these 12 candidate genes revealed a G to A base substitution in the fourth exon of LOC_Os07g30510, a putative cysteine-rich receptor-like kinase (CRK), which led to an amino acid change (Val 429 to Ile) in the LIL1 protein. Comparison of the transcript accumulation of the 12 candidate genes between LIL1 and 93-11 revealed that LOC_Os07g30510 was up-regulated significantly in LIL1 . Overexpression of the LOC_Os07g30510 gene from LIL1 induced a LIL1 -like lesion phenotype in Nipponbare. Thus, LIL1 is a novel LMM in rice that will facilitate the further study of the molecular mechanisms of HR and the rice blast resistance.

  13. Hippocampus lesions induced deficits in social and spatial recognition in Octodon degus.

    Science.gov (United States)

    Uekita, Tomoko; Okanoya, Kazuo

    2011-06-01

    Previous studies of rodents reported that the hippocampus plays an important role in social behavior as well as spatial behavior. However, there are inconsistencies between reports of the effects of hippocampal lesions on social behavior. The present study sought to clarify the aspects of social behavior in which the hippocampus plays a role in the degu, Octodon degus, a social rodent. We examined the effects of hippocampal lesions on social behavior in the degu using familiar and novel partners. When placed in a familiar environment with a familiar partner after surgery, sham operation control (S.Cont) degus exhibited affinitive behavior longer compared with hippocampal lesioned (HPC) degus. In a novel environment, S.Cont degus exhibited longer aggressive behavior toward novel partners, and longer affinitive behavior with familiar partners compared with HPC degus. HPC degus did not show evidence of differentiation in social behavior, regardless of partner's novelty. The results of an anxiety test confirmed that these findings could not be attributed to changes in emotional state. We conducted an object-recognition test with the same subjects. HPC degus showed an impairment in spatial recognition but not object recognition. Taken together, these results suggest that the degu hippocampus plays an important role not only in spatial recognition but also social recognition. The changes in social behavior resulting from hippocampal lesions were interpreted as due to an impairment of social recognition rather than an impairment in novelty detection. Copyright © 2011 Elsevier B.V. All rights reserved.

  14. Lesion-induced increase in survival and migration of human neural progenitor cells releasing GDNF

    Science.gov (United States)

    Behrstock, Soshana; Ebert, Allison D.; Klein, Sandra; Schmitt, Melanie; Moore, Jeannette M.; Svendsen, Clive N.

    2009-01-01

    The use of human neural progenitor cells (hNPC) has been proposed to provide neuronal replacement or astrocytes delivering growth factors for brain disorders such as Parkinson’s and Huntington’s disease. Success in such studies likely requires migration from the site of transplantation and integration into host tissue in the face of ongoing damage. In the current study, hNPC modified to release glial cell line derived neurotrophic factor (hNPCGDNF) were transplanted into either intact or lesioned animals. GDNF release itself had no effect on the survival, migration or differentiation of the cells. The most robust migration and survival was found using a direct lesion of striatum (Huntington’s model) with indirect lesions of the dopamine system (Parkinson’s model) or intact animals showing successively less migration and survival. No lesion affected differentiation patterns. We conclude that the type of brain injury dictates migration and integration of hNPC which has important consequences when considering transplantation of these cells as a therapy for neurodegenerative diseases. PMID:19044202

  15. Lithium-induced Nephrotoxicity: A Case Report of Renal Cystic Disease Presenting as a Mass Lesion

    Directory of Open Access Journals (Sweden)

    Yvonne McCartney

    2014-11-01

    Full Text Available Lithium is an effective therapeutic agent used in the management of bipolar disorder. However, lithium is also associated with several side effects, including renal toxicity. We present a case of a symptomatic cystic mass lesion in the kidney of a patient who had a history of lithium therapy for the management of bipolar disorder.

  16. Regulation of GABA and benzodiazepine receptors following neurotoxin-induced striatal and medial forebrain bundle lesions

    International Nuclear Information System (INIS)

    Pan, H.S.I.

    1985-01-01

    GABA, a major inhibitory transmitter, is used by many projection neurons of the striatum. To investigate the role of GABA in striatal function, the GABA receptor complex was studied after lesions of the striatum or the nigrostriatal neurons. Quantitative receptor autoradiography using thaw-mounted tissue slices was developed for the study of GABA and benzodiazepine (BDZ) receptors. With the technique established, binding to GABA and BDZ receptors after unilateral striatal kainate lesions was examined. Subsequently, changes in GABA and BDZ receptors were studied following the destruction of dopaminergic nigrostriatal cells by unilateral 6-hydroxydopamine lesion of the medial forebrain bundle. In summary, quantitative receptor autoradiography allowed the detection of GABA and BDZ receptor changes in multiple small areas in each lesioned brain. This technique made it feasible to carry out kinetic saturation, and competition studies using less than 1 mg of tissue. The data suggest that dopamine is functionally inhibitory on striatopallidal neurons but is functionally excitatory on striatoentopeduncular and striatonigral cells which in turn inhibit the thalamus. This quantitative autoradiographic technique can be generalized to study other transmitter receptors and can be combined with 2-deoxyglucose uptake studies

  17. Distribution and differential expression of microRNAs in the intestinal mucosal layer of necrotic enteritis induced Fayoumi chickens

    Directory of Open Access Journals (Sweden)

    Deivendran Rengaraj

    2017-07-01

    Full Text Available Objective Despite an increasing number of investigations into the pathophysiology of necrotic enteritis (NE disease, etiology of NE-associated diseases, and gene expression profiling of NE-affected tissues, the microRNA (miRNA profiles of NE-affected poultry have been poorly studied. The aim of this study was to induce NE disease in the genetically disparate Fayoumi chicken lines, and to perform non-coding RNA sequencing in the intestinal mucosal layer. Methods NE disease was induced in the Fayoumi chicken lines (M5.1 and M15.2, and non-coding RNA sequencing was performed in the intestinal mucosal layer of both NE-affected and uninfected chickens to examine the differential expression of miRNAs. Next, quantitative real-time polymerase chain reaction (real-time qPCR was performed to further examine four miRNAs that showed the highest fold differences. Finally, bioinformatics analyses were performed to examine the four miRNAs target genes involvement in the signaling pathways, and to examine their interaction. Results According to non-coding RNA sequencing, total 50 upregulated miRNAs and 26 downregulated miRNAs were detected in the NE-induced M5.1 chickens. While 32 upregulated miRNAs and 11 downregulated miRNAs were detected in the NE-induced M15.2 chickens. Results of real-time qPCR analysis on the four miRNAs (gga-miR-9-5p, gga-miR-20b-5p, gga-miR-196-5p, and gga-let-7d were mostly correlated with the results of RNAseq. Overall, gga-miR-20b-5p was significantly downregulated in the NE-induced M5.1 chickens and this was associated with the upregulation of its top-ranking target gene, mitogen-activated protein kinase, kinase 2. Further bioinformatics analyses revealed that 45 of the gene targets of gga-miR-20b-5p were involved in signal transduction and immune system-related pathways, and 35 of these targets were predicted to interact with each other. Conclusion Our study is a novel report of miRNA expression in Fayoumi chickens, and could be

  18. Downregulation of hepatic and intestinal ATP-binding-cassette transporters abcg5 and abcg8 expression associated with altered sterol fluxes in rats with streptozotocin-induced diabetes

    NARCIS (Netherlands)

    Bloks, VW; Bakker-van Waarde, WW; Verkade, HJ; Kema, IP; Havinga, R; Wolters, H; Schaap, FG; Sauer, PJJ; Vink, E; Groen, AK; Kuipers, F

    ABSTRACT: P234 Downregulation of Hepatic and Intestinal ATP-Binding-Cassette Transporters Abcg5 and Abcg8 Expression Associated with Altered Sterol Fluxes in Rats with Streptozotocin-Induced Diabetes Vincent W. Bloks, Willie W. Bakker-van Waarde, Henkjan J. Verkade, Ido P. Kema, Rick Havinga, Henk

  19. Opposite effect of oxidative stress on inducible nitric oxide synthase and haem oxygenase-1 expression in intestinal inflammation: anti-inflammatory effect of carbon monoxide

    NARCIS (Netherlands)

    Dijkstra, Gerard; Blokzijl, Hans; Bok, Lisette; Homan, Manon; van Goor, Harry; Faber, Klaas Nico; Jansen, Peter L. M.; Moshage, Han

    2004-01-01

    Inducible nitric oxide synthase (iNOS) is expressed in intestinal epithelial cells (IEC) of patients with active inflammatory bowel disease (IBD) and in IEC of endotoxaemic rats. The induction of iNOS in IEC is an element of the NF-kappaB-mediated survival pathway. Haem oxygenase-1 (HO-1) is an

  20. Targeted delivery of antigen to intestinal dendritic cells induces oral tolerance and prevents autoimmune diabetes in NOD mice.

    Science.gov (United States)

    Chen, Yulin; Wu, Jie; Wang, Jiajia; Zhang, Wenjing; Xu, Bohui; Xu, Xiaojun; Zong, Li

    2018-03-15

    The intestinal immune system is an ideal target to induce immune tolerance physiologically. However, the efficiency of oral protein antigen delivery is limited by degradation of the antigen in the gastrointestinal tract and poor uptake by antigen-presenting cells. Gut dendritic cells (DCs) are professional antigen-presenting cells that are prone to inducing antigen-specific immune tolerance. In this study, we delivered the antigen heat shock protein 65-6×P277 (H6P) directly to the gut DCs of NOD mice through oral vaccination with H6P-loaded targeting nanoparticles (NPs), and investigated the ability of this antigen to induce immune tolerance to prevent autoimmune diabetes in NOD mice. A targeting NP delivery system was developed to encapsulate H6P, and the ability of this system to protect and facilitate H6P delivery to gut DCs was assessed. NOD mice were immunised with H6P-loaded targeting NPs orally once a week for 7 weeks and the onset of diabetes was assessed by monitoring blood glucose levels. H6P-loaded targeting NPs protected the encapsulated H6P from degradation in the gastrointestinal tract environment and significantly increased the uptake of H6P by DCs in the gut Peyer's patches (4.1 times higher uptake compared with the control H6P solution group). Oral vaccination with H6P-loaded targeting NPs induced antigen-specific T cell tolerance and prevented diabetes in 100% of NOD mice. Immune deviation (T helper [Th]1 to Th2) and CD4 + CD25 + FOXP3 + regulatory T cells were found to participate in the induction of immune tolerance. In this study, we successfully induced antigen-specific T cell tolerance and prevented the onset of diabetes in NOD mice. To our knowledge, this is the first attempt at delivering antigen to gut DCs using targeting NPs to induce T cell tolerance.

  1. Examinations on cases of surgery for radiation-induced disorders of large intestine

    Energy Technology Data Exchange (ETDEWEB)

    Shiba, Tadaaki [Toho Univ., Tokyo (Japan). School of Medicine

    1996-11-01

    Author`s experience of surgery for radiation colitis was examined and discussed on the primary disease, radiation dose, major symptoms, surgical techniques, results and post-operative complication. Patients were 1 male and 21 females of the average age of 59.5 y. The primary diseases were bladder cancer for the male and uterine cancer for the females. The radiation dose ranged from 35-120 Gy and was 63.4 Gy in a mean. The symptoms for surgery were 14 ileuses, 4 intestinal hemorrhages, 1 perforation and 3 burrows. Colostomy was performed for 18 cases; enterostomy, 2; anastomosis, 1; and enterectomy, 1, which resulted in improvement of symptoms in 5 cases, 0, 1 and 1, respectively. The author concluded that radiation colitis should be treated preventively. (K.H.)

  2. Volvulus as a complication of chronic intestinal pseudo-obstruction syndrome

    NARCIS (Netherlands)

    de Betue, Carlijn T.; Boersma, Doeke; Oomen, Matthijs W.; Benninga, Marc A.; de Jong, Justin R.

    2011-01-01

    Chronic intestinal pseudo-obstruction syndrome (CIPS) is a severe motility disorder of the gastrointestinal tract that presents with continuous or recurrent symptoms and signs of intestinal obstruction without evidence of a structural lesion occluding the intestinal lumen. Mechanical obstruction

  3. Pyrimidine dimers are not the principal pre-mutagenic lesions induced in lambda phage DNA by ultraviolet light

    International Nuclear Information System (INIS)

    Wood, R.D.

    1985-01-01

    Experiments were performed to examine the role of cyclobutyl pyrimidine dimers in the process of mutagenesis by ultraviolet light. Lambda phage DNA was irradiated with u.v. and then incubated with an Escherichia coli photoreactivating enzyme, which monomerizes cyclobutyl pyrimidine dimers upon exposure to visible light. The photoreactivated DNA was packaged into lambda phage particles, which were used to infect E. coli uvr - host cells that had been induced for SOS functions by ultraviolet irradiation. Photoreactivation removed most toxic lesions from irradiated phage, but did not change the frequency of induction of mutations to the clear-plaque phenotype. This implies that cyclobutyl pyrimidine dimers can be lethal, but usually do not serve as sites of mutations in the phage. The DNA sequences of mutants, derived from photoreactivated DNA showed that almost two-thirds (16/28) were transitions, the same fraction found for u.v. mutagenesis without photoreactivation. Thus the lesion inducing transitions is not the cyclobutyl pyrimidine dimer. Photoreactivation of SOS-induced host cells before infection with u.v.-irradiated phage reduced mutagenesis substantially. In this case, photoreversal of cyclobutyl dimers serves to reduce expression of the SOS functions that are required in targeted u.v. mutagenesis. (author)

  4. Comparative pathogenesis of radium-induced intracortical bone lesions in humans and beagles

    International Nuclear Information System (INIS)

    Pool, R.R.; Morgan, J.P.; Parks, N.J.; Farnham, J.E.; Littman, M.S.

    1982-01-01

    An interlaboratory research team from our Laboratory and the Center for Human Radiobiology at Argonne National Laboratory has performed an initial comparison of intracortical lesions in the long bones of dog and man following chronic radium deposition in the skeleton. The sequential radiographic appearance and morphology of radiation osteodystrophy is discussed. The role of osteodystrohy in the evaluation of bone tumors in the dog is examined

  5. On the biophysical interpretation of lethal DNA lesions induced by ionising radiation

    Czech Academy of Sciences Publication Activity Database

    Kundrát, Pavel; Stewart, R.D.

    2006-01-01

    Roč. 122, 1-4 (2006), s. 169-172 ISSN 0144-8420 R&D Projects: GA ČR GA202/05/2728 Institutional research plan: CEZ:AV0Z10100502 Keywords : clustered DNA lesions * V79 cells * proton tracks * DNA damage * DNA repair * radiobiological modelling Subject RIV: BF - Elementary Particles and High Energy Physics Impact factor: 0.446, year: 2006

  6. Indication of the radiofrequency induced lesion size by pre-ablation measurements

    DEFF Research Database (Denmark)

    Stagegaard, Niels; Petersen, Helen Høgh; Chen, Xu

    2005-01-01

    BACKGROUND: During radiofrequency ablation of arrhythmias tissue heating and hence lesion size depend on electrode-tissue contact and cooling of the electrode tip caused by cavitary blood flow. These factors are unique and unknown for each catheter placement in the beating heart. A tool for asses......BACKGROUND: During radiofrequency ablation of arrhythmias tissue heating and hence lesion size depend on electrode-tissue contact and cooling of the electrode tip caused by cavitary blood flow. These factors are unique and unknown for each catheter placement in the beating heart. A tool...... for assessing these factors prior to ablation may indicate the lesion size which will be obtained for any given catheter position. METHODS AND RESULTS: Radiofrequency ablation was performed in vitro on strips of left ventricular porcine myocardium during two different levels of convective cooling (0 or 0.1 m....../s), two different contact pressures (10 or 30 g) and parallel or perpendicular electrode-tissue orientation using 7F 4 mm tip catheters. Prior to ablation the impedance rise (DeltaIMP) caused by the obtained contact and the temperature rise with a 0.6 W 5 s test pulse (DeltaT) were measured. Subsequently...

  7. New biomarkers for increased intestinal permeability induced by dextran sodium sulphate and fasting in chickens.

    Science.gov (United States)

    Gilani, S; Howarth, G S; Kitessa, S M; Tran, C D; Forder, R E A; Hughes, R J

    2017-10-01

    Increased intestinal permeability (IP) can lead to compromised health in chickens. As there is limited literature on in vivo biomarkers to assess increased IP in chickens, the objective of this study was to identify a reliable biomarker of IP using DSS ingestion and fasting models. Male Ross chickens (n = 48) were reared until day 14 on the floor pen in an animal care facility, randomized into the following groups: control, DSS and fasting (each with n = 16), and then placed in metabolism cages. DSS was administered in drinking water at 0.75% from days 16 to 21, while controls and fasted groups received water. All birds had free access to feed and water except the birds in the fasting group that were denied feed for 19.5 h on day 20. On day 21, all chickens were given two separate oral gavages comprising fluorescein isothiocyanate dextran (FITC-d, 2.2 mg in 1 ml/bird) at time zero and lactulose, mannitol and rhamnose (LMR) sugars (0.25 g L, 0.05 g M and 0.05 g R in 2 ml/bird) at 60 min. Whole blood was collected from the brachial vein in a syringe 90 min post-LMR sugar gavage. Serum FITC-d and plasma LMR sugar concentrations were measured by spectrophotometry and high-performance ion chromatography respectively. Plasma concentrations of intestinal fatty acid binding protein, diamine oxidase, tight junction protein (TJP), d-lactate and faecal α-antitrypsin inhibitor concentration were also analysed by ELISA. FITC-d increased significantly (p fasting compared with control. L/M and L/R ratios for fasting and L/M ratio for DSS increased compared with control chickens (p fasting but not DSS treatment, compared with controls. Other tests did not indicate changes in IP (p > 0.05). We concluded that FITC-d and LMR sugar tests can be used in chickens to assess changes in IP. Journal of Animal Physiology and Animal Nutrition © 2016 Blackwell Verlag GmbH.

  8. Synthesis of modified oligonucleotides for repair and replication studies of single and double radio-induced DNA lesions

    International Nuclear Information System (INIS)

    Muller, E.

    2002-01-01

    Several oxidative processes induce the formation of DNA lesions. In order to evaluate the biological and structural significance of such damage, several DNA lesions were inserted into synthetic oligonucleotides at defined sites. The research work aimed at describing the preparation of oligonucleotides t hat contained DNA damage and the evaluation of the biological properties of the lesions. A first part described the incorporation of radiation-induced lesions, namely (5'S,6S)-5',6-cyclo-5,6-dihydro-2'-deoxyuridine and (5'S,5S,6S)-5',6-cyclo-5-hydroxy-5,6-dihydro-2'-desoxyuridine into oligonucleotides. The modified DNA fragments were characterised by several spectroscopic and biochemical analyses including ESI MS, MALDI-TOF MS, CLHP and enzymatic digestions. During in vitro DNA synthesis by Taq DNA polymerase and Klenow exo fragment, the pyrimidine cyclo-nucleosides were found to block the progression of the enzymes. Then, repair studies by ADN N glycosylases, operating in the base excision repair pathway, have shown that the anhydro-nucleoside lesions were not recognised nor excised by Fpg, endo III, endo VIII, yNtg1 yNtg2 and yOgg1. Interestingly, the Latococcus lactis Fpg protein recognises (formation of a non covalent complex) but do not excise the damage. The incorporation into oligonucleotides of the (5R*) and (5S*) diastereoisomers of 1-[2-deoxy-β-D-erythro-pentofuranosyl]-5-hydroxy-hydantoin, generated by several oxidative processes was then described. In vitro DNA replication assays using modified oligonucleotides matrix showed a lethal potential of the latter base damage. Repair studies by ADN N-glycosylases showed that the damage was substrate for Fpg, endo III, endo VIII, Ntg1, Ntg2 and Fpg-L1. The rates of excision as inferred from the determination of the Michaelis kinetics constants were found to be affected by the presence of the damage. MALDI-TOF MS was used in order to gain insights into mechanistic aspects of oligonucleotides cleavage by the

  9. Intestinal lesions in pigs affected with postweaning multisystemic wasting syndrome Lesões entéricas em suínos afetados por síndrome multissistêmica do definhamento dos suínos

    Directory of Open Access Journals (Sweden)

    Priscila Zlotowski

    2008-06-01

    Full Text Available Samples of mesenteric lymph nodes and intestines from 79 unthrifty 3- to 5-month-old postweaning pigs, confirmed as naturally affected with postweaning multisystemic wasting syndrome (PMWS, were studied. Pigs originated from 12 farms in southern Brazil and were selected on the basis of clinical signs and/or gross lesions suggestive of enteric disorder. Lymphohistiocytic infiltrates of varying intensity were associated with anti-porcine circovirus type 2 (anti-PCV2 immunostaining (IS in samples of intestines and mesenteric lymph nodes from all pigs. Although most findings were similar to those described in PCV2-associated enteritis, anti-PCV2 IS in association with depletion of the goblet cell mucin stores (24 pigs, diffuse ileal villous atrophy and fusion (18 pigs, and dilatation of the lymphatic vessels (11 pigs combined or not with lymphangitis were also observed. PCV2 antigen was immunohistochemically demonstrated in the cytoplasm and nuclei from intralesional epithelial cells, histiocytes, and endothelial-like cells in intestinal tissues. Together these findings imply an association with PCV2. The presence of co-infections by Lawsonia intracellularis, Brachyspira spp., Mycobacterium spp., Salmonella spp., rotavirus, parvovirus, coronavirus and enteric calicivirus with PCV2 in the intestinal lesions was investigated.Amostras de linfonodos mesentéricos e intestinos de 79 leitões desmamados refugos, entre 3 e 5 meses de idade e confirmados como naturalmente afetados pela síndrome multissistêmica do definhamento foram estudadas. Os suínos eram oriundos de 12 criações no sul do país e foram selecionados em função dos sinais clínicos e/ou lesões macroscópicas sugestivos de doença entérica. Infiltrados linfoistiocíticos de intensidades variáveis foram associados com marcação positiva anti-circovirus suíno tipo 2 (anti-PCV2 em amostras de intestinos e linfonodos mesentéricos de todos os 79 animais. Embora a maioria dos achados

  10. Light/Dark Shifting Promotes Alcohol-Induced Colon Carcinogenesis: Possible Role of Intestinal Inflammatory Milieu and Microbiota

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    Faraz Bishehsari

    2016-12-01

    Full Text Available Background: Colorectal cancer (CRC is associated with the modern lifestyle. Chronic alcohol consumption—a frequent habit of majority of modern societies—increases the risk of CRC. Our group showed that chronic alcohol consumption increases polyposis in a mouse mode of CRC. Here we assess the effect of circadian disruption—another modern life style habit—in promoting alcohol-associated CRC. Method: TS4Cre × adenomatous polyposis coli (APClox468 mice underwent (a an alcohol-containing diet while maintained on a normal 12 h light:12 h dark cycle; or (b an alcohol-containing diet in conjunction with circadian disruption by once-weekly 12 h phase reversals of the light:dark (LD cycle. Mice were sacrificed after eight weeks of full alcohol and/or LD shift to collect intestine samples. Tumor number, size, and histologic grades were compared between animal groups. Mast cell protease 2 (MCP2 and 6 (MCP6 histology score were analyzed and compared. Stool collected at baseline and after four weeks of experimental manipulations was used for microbiota analysis. Results: The combination of alcohol and LD shifting accelerated intestinal polyposis, with a significant increase in polyp size, and caused advanced neoplasia. Consistent with a pathogenic role of stromal tryptase-positive mast cells in colon carcinogenesis, the ratio of mMCP6 (stromal/mMCP2 (intraepithelial mast cells increased upon LD shifting. Baseline microbiota was similar between groups, and experimental manipulations resulted in a significant difference in the microbiota composition between groups. Conclusions: Circadian disruption by Light:dark shifting exacerbates alcohol-induced polyposis and CRC. Effect of circadian disruption could, at least partly, be mediated by promoting a pro-tumorigenic inflammatory milieu via changes in microbiota.

  11. Prefrontal cortex or basolateral amygdala lesions blocked the stress-induced inversion of serial memory retrieval pattern in mice.

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    Chauveau, F; Piérard, C; Coutan, M; Drouet, I; Liscia, P; Béracochéa, D

    2008-09-01

    Previous data from our team have shown that pre-test stress in mice reversed the pattern of memory retrieval in a contextual serial spatial task (CSD; Celerier, A., Pierard, C., Rachbauer, D., Sarrieau, A., & Beracochea, D. (2004). Contextual and serial discriminations: A new learning paradigm to assess simultaneously the effects of acute stress on retrieval of flexible or stable information in mice. Learning and Memory, 11, 196-204). The present study is aimed at determining brain areas which might be critically involved in mediating the stress effect on memory retrieval in the CSD task. For that purpose, we studied hereby the effects of ibotenic acid lesions of either the prefrontal cortex (PFC) or the basolateral amygdala (BLA) in Stressed or Non-Stressed Balb/c mice on memory retrieval in the CSD task. In that task, mice learned two successive spatial discriminations (D1 and D2) within two different internal contexts in a four-hole board. The stressor (electric footshocks) was delivered 5 min before test, occurring 24 h after acquisition. During test, mice were relocated either on the floor of the first or of the second discrimination. Results showed that (i) spatial memory was substantial and remained unaffected both by lesions and stress; (ii) Non-Stressed controls as well as Non-Stressed or Stressed PFC and BLA-lesioned mice remembered accurately D1 but not D2; and (iii) in contrast, Stressed controls accurately remembered D2 but not D1. In parallel to behavioral experiments, we also showed that PFC and BLA lesions did not affect the stress-induced increase of plasma corticosterone levels. All together, PFC and BLA integrity are not necessary for retrieval processes per se; in contrast, the PFC and BLA are critically involved in the mediation of the deleterious stress effects on serial order memory retrieval.

  12. Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol

    International Nuclear Information System (INIS)

    Miller, M.J.; Zhang, x.J.; Gu, x.A.; Clark, D.A.

    1991-01-01

    Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of 51 Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in 51 Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal 51 Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol

  13. Acute intestinal injury induced by acetic acid and casein: prevention by intraluminal misoprostol

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    Miller, M.J.; Zhang, x.J.; Gu, x.A.; Clark, D.A. (Department of Pediatrics, Louisiana State University School of Medicine, New Orleans (USA))

    1991-07-01

    Acute injury was established in anesthetized rabbits by intraluminal administration of acetic acid with and without bovine casein, into loops of distal small intestine. Damage was quantified after 45 minutes by the blood-to-lumen movement of {sup 51}Cr-labeled ethylenediaminetetraacetic acid (EDTA) and fluorescein isothiocyanate-tagged bovine serum albumin as well as luminal fluid histamine levels. The amount of titratable acetic acid used to lower the pH of the treatment solutions to pH 4.0 was increased by the addition of calcium gluconate. Luminal acetic acid caused a 19-fold increase in {sup 51}Cr-EDTA accumulation over saline controls; casein did not modify this effect. In saline controls, loop fluid histamine levels bordered on the limits of detection (1 ng/g) but were elevated 19-fold by acetic acid exposure and markedly increased (118-fold) by the combination of acid and casein. Intraluminal misoprostol (3 or 30 micrograms/mL), administered 30 minutes before acetic acid, significantly attenuated the increase in epithelial permeability (luminal {sup 51}Cr-EDTA, fluorescein isothiocyanate-bovine serum albumin accumulation) and histamine release (P less than 0.05). Diphenhydramine, alone or in combination with cimetidine, and indomethacin (5 mg/kg IV) were not protective. It is concluded that exposure of the epithelium to acetic acid promotes the transepithelial movement of casein leading to enhanced mast cell activation and mucosal injury. Damage to the epithelial barrier can be prevented by misoprostol.

  14. The role of the small intestine in the development of dietary fat-induced obesity and insulin resistance in C57BL/6J mice

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    Bromhaar Mechteld

    2008-05-01

    Full Text Available Abstract Background Obesity and insulin resistance are two major risk factors underlying the metabolic syndrome. The development of these metabolic disorders is frequently studied, but mainly in liver, skeletal muscle, and adipose tissue. To gain more insight in the role of the small intestine in development of obesity and insulin resistance, dietary fat-induced differential gene expression was determined along the longitudinal axis of small intestines of C57BL/6J mice. Methods Male C57BL/6J mice were fed a low-fat or a high-fat diet that mimicked the fatty acid composition of a Western-style human diet. After 2, 4 and 8 weeks of diet intervention small intestines were isolated and divided in three equal parts. Differential gene expression was determined in mucosal scrapings using Mouse genome 430 2.0 arrays. Results The high-fat diet significantly increased body weight and decreased oral glucose tolerance, indicating insulin resistance. Microarray analysis showed that dietary fat had the most pronounced effect on differential gene expression in the middle part of the small intestine. By overrepresentation analysis we found that the most modulated biological processes on a high-fat diet were related to lipid metabolism, cell cycle and inflammation. Our results further indicated that the nuclear receptors Ppars, Lxrs and Fxr play an important regulatory role in the response of the small intestine to the high-fat diet. Next to these more local dietary fat effects, a secretome analysis revealed differential gene expression of secreted proteins, such as Il18, Fgf15, Mif, Igfbp3 and Angptl4. Finally, we linked the fat-induced molecular changes in the small intestine to development of obesity and insulin resistance. Conclusion During dietary fat-induced development of obesity and insulin resistance, we found substantial changes in gene expression in the small intestine, indicating modulations of biological processes, especially related to lipid

  15. Effects of stress on gastrointestinal function: interactions of neural and endocrine systems in mediating stress-induced intestinal dysfunction in rats

    International Nuclear Information System (INIS)

    Williams, C.L.

    1987-01-01

    The etiology of stress-induced intestinal dysfunction is completely unresolved, and the lack of an appropriate animal model has hindered studies of causality. We compared a number of stressors and their resultant effects on intestinal transit, a measure of the propulsive motor activity of the gut, in the rat. We found that the response of the intestine to stress, and the neural systems activated by stress, were dependent on the type and duration of stress, as well as the animal strain, and gender. We developed a model, acute wrapping restraint stress, to fully characterize the effects of stress on intestinal transit. Wrap restraint stress is a nonulcerogenic model in which rats are subjected to acute restraint by wrapping them in a harness of paper tape to restrict, but not prevent movement of the upper body and forelimbs. Transit was evaluated by the geometric center method, in which a radiomarker ( 51 Cr) is instilled directly into the proximal duodenum and proximal colon via a surgically placed intestinal cannula, in fasted, adult female Sprague Dawley rats

  16. Protective Effects of Bifidobacterium on Intestinal Barrier Function in LPS-Induced Enterocyte Barrier Injury of Caco-2 Monolayers and in a Rat NEC Model.

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    Ling, Xiang; Linglong, Peng; Weixia, Du; Hong, Wei

    2016-01-01

    Zonulin protein is a newly discovered modulator which modulates the permeability of the intestinal epithelial barrier by disassembling intercellular tight junctions (TJ). Disruption of TJ is associated with neonatal necrotizing enterocolitis (NEC). It has been shown bifidobacterium could protect the intestinal barrier function and prophylactical administration of bifidobacterium has beneficial effects in NEC patients and animals. However, it is still unknown whether the zonulin is involved in the gut barrier dysfunction of NEC, and the protective mechanisms of bifidobacterium on intestinal barrier function are also not well understood. The present study aims to investigate the effects of bifidobacterium on intestinal barrier function, zonulin regulation, and TJ integrity both in LPS-induced enterocyte barrier injury of Caco-2 monolayers and in a rat NEC model. Our results showed bifidobacterium markedly attenuated the decrease in transepithelial electrical resistance and the increase in paracellular permeability in the Caco-2 monolayers treated with LPS (P zonulin release (P zonulin (P zonulin protein release and improvement of intestinal TJ integrity.

  17. A mixture of Lactobacillus species isolated from traditional fermented foods promote recovery from antibiotic-induced intestinal disruption in mice.

    Science.gov (United States)

    Shi, Y; Zhao, X; Zhao, J; Zhang, H; Zhai, Q; Narbad, A; Chen, W

    2018-03-01

    This study evaluated the antibiotic-induced changes in microbial ecology, intestinal dysbiosis and low-grade inflammation; and the combined effect of four different Lactobacillus species on recovery of microbiota composition and improvement of gut barrier function in mice. Administration of the antibiotic ampicillin for 2 weeks decreased microbial community diversity, induced caecum tumefaction and increased gut permeability in mice. Application of a probiotic cocktail of four Lactobacillus species (JUP-Y4) modulated the microbiota community structure and promoted the abundance of potentially beneficial bacteria such as Akkermansia. Ampicillin administration led to a decline in Bacteroidetes from 46·6 ± 3·91% to 0·264 ± 0·0362%; the addition of JUP-Y4 restored this to 41·4 ± 2·87%. This probiotic supplementation was more effective than natural restoration, where the levels of Bacteroidetes were only restored to 29·3 ± 2·07%. Interestingly, JUP-Y4 treatment was more effective in the restoration of microbiota in faecal samples than in caecal samples. JUP-Y4 also significantly reduced the levels of d-lactate and endotoxin (lipopolysaccharide, LPS) in the serum of mice, and increased the expression of tight-junction proteins while reducing the production of inflammatory cytokines (TNF-α, IL-6, MCP-1, IFN-γ and IL-1β) in the ileum and the colon of antibiotic-treated mice. JUP-Y4 not only promoted recovery from antibiotic-induced gut dysbiosis, but also enhanced the function of the gut barrier, reduced inflammation and lowered levels of circulating endotoxin in mice. Consumption of a mixture of Lactobacillus species may encourage faster recovery from antibiotic-induced gut dysbiosis and gut microbiota-related immune disturbance. © 2018 The Society for Applied Microbiology.

  18. Amebiasis intestinal Intestinal amebiasis

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    JULIO CÉSAR GÓMEZ

    2007-03-01

    Full Text Available Entamoeba histolytica es el patógeno intestinal más frecuente en nuestro medio -después de Giardia lamblia-, una de las principales causas de diarrea en menores de cinco años y la cuarta causa de muerte en el mundo debida a infección por protozoarios. Posee mecanismos patogénicos complejos que le permiten invadir la mucosa intestinal y causar colitis amebiana. El examen microscópico es el método más usado para su identificación pero la existencia de dos especies morfológicamente iguales, una patógena ( E. histolytica y una no patógena ( Entamoeba dispar, ha llevado al desarrollo de otros métodos de diagnóstico. El acceso al agua potable y los servicios sanitarios adecuados, un tratamiento médico oportuno y el desarrollo de una vacuna, son los ejes para disminuir la incidencia y mortalidad de esta entidad.Entamoeba histolytica is the most frequent intestinal pathogen seen in our country, after Giardia lamblia, being one of the main causes of diarrhea in children younger than five years of age, and the fourth leading cause of death due to infection for protozoa in the world. It possesses complex pathogenic mechanisms that allow it to invade the intestinal mucosa, causing amoebic colitis. Microscopy is the most used method for its identification, but the existence of two species morphologically identical, the pathogen one ( E. histolytica, and the non pathogen one ( E. dispar, have taken to the development of other methods of diagnosis. The access to drinkable water and appropriate sanitary services, an opportune medical treatment, and the development of a vaccine are the axes to diminish the incidence and mortality of this entity.

  19. TLR2/TLR4 activation induces Tregs and suppresses intestinal inflammation caused by Fusobacterium nucleatum in vivo.

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    Yin-Ping Jia

    Full Text Available Toll-like receptors (TLRs 2 and 4 play critical roles in intestinal inflammation caused by Fusobacterium nucleatum (F. nucleatum infection, but the role of TLR2/TLR4 in regulation of proinflammatory cytokines remains unknown. In this study, through microarray analysis and qRT-PCR, we showed that TLR2/TLR4 are involved in the F. nucleatum-induced inflammatory signaling pathway in Caco-2 cells, C57BL/6 mice and human clinical specimens. In TLR2-/- and TLR4-/- mice, F. nucleatum infection resulted in increased colonization of the bacteria and production of the proinflammatory cytokines IL-8, IL-1β and TNF-α. In addition, the ratio of Foxp3+ CD4+ T cells in the total CD4+ T cells in TLR2-/- and TLR4-/- mice was less than that in wild-type mice, and the ratio in hybrid mice was more than that in knockout mice, which suggested that TLR2/TLR4 mediated the number of Tregs. Furthermore, it was observed that inflammatory cytokine levels were reduced in TLR2-/- mice after Treg transfer. Thus, these data indicate that TLR2/TLR4 regulate F. nucleatum-induced inflammatory cytokines through Tregs in vivo.

  20. The Bacterial Species Campylobacter jejuni Induce Diverse Innate Immune Responses in Human and Avian Intestinal Epithelial Cells

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    Daniel A. John

    2017-09-01

    Full Text Available Campylobacter remain the major cause of human gastroenteritis in the Developed World causing a significant burden to health services. Campylobacter are pathogens in humans and chickens, although differences in mechanistic understanding are incomplete, in part because phenotypic strain diversity creates inconsistent findings. Here, we took Campylobacter jejuni isolates (n = 100 from multi-locus sequence typed collections to assess their pathogenic diversity, through their inflammatory, cytotoxicity, adhesion, invasion and signaling responses in a high-throughput model using avian and human intestinal epithelial cells. C. jejuni induced IL-8 and CXCLi1/2 in human and avian epithelial cells, respectively, in a MAP kinase-dependent manner. In contrast, IL-10 responses in both cell types were PI 3-kinase/Akt-dependent. C. jejuni strains showed diverse levels of invasion with high invasion dependent on MAP kinase signaling in both cell lines. C. jejuni induced diverse cytotoxic responses in both cell lines with cdt-positive isolates showing significantly higher toxicity. Blockade of endocytic pathways suggested that invasion by C. jejuni was clathrin- and dynamin-dependent but caveolae- independent in both cells. In contrast, IL-8 (and CXCLi1/2 production was dependent on clathrin, dynamin, and caveolae. This study is important because of its scale, and the data produced, suggesting that avian and human epithelial cells use similar innate immune pathways where the magnitude of the response is determined by the phenotypic diversity of the Campylobacter species.

  1. The prevention of radiation-induced DNA damage and apoptosis in human intestinal epithelial cells by salvianic acid A

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    Yanjun Zhang

    2014-07-01

    Full Text Available The topic of radiation always provokes public debate, and the uses of radiation for therapeutic and other purposes have always been associated with some anxiety. Salvia miltiorrhiza Bunge has been widely used for the treatment of various diseases including cerebrovascular diseases, coronary artery diseases, and myocardial infarction. Salvianolic acid A (SAA d (+-(3,4-dihydroxyphenyl lactic acid is the principal effective, watersoluble constituent of Salvia miltiorrhiza Bunge. In our present study, radiation-induced DNA damage and apoptosis in human intestinal epithelial cells (HIEC in the presence and absence of SAA were examined. We investigated the effects of SAA on ROS formation and the activity of enzymatic antioxidants (SOD, the lipid peroxidative index and the levels of non-enzymatic antioxidant (GSH. Finally, we investigated whether the reduction of radiation-induced cell death caused by SAA might be related to mitochondria-dependent apoptosis. Present findings indicate that SAA is a promising radioprotective agent with a strong antioxidant activity. SAA exerted its protective action on the proliferative activity of HIEC cells as evidenced by decreased cytotoxicity after exposure to γ-radiation. It is possible that SAA achieved its radioprotective action, at least in part, by enhancing DNA repair and the activity of antioxidant enzymes, by scavenging ROS and by inhibiting the mitochondria-dependent apoptotic pathway.

  2. Pathological Lesions and Inducible Nitric Oxide Synthase Expressions in the Liver of Mice Experimentally Infected with Clonorchis sinensis.

    Science.gov (United States)

    Yang, Qing-Li; Shen, Ji-Qing; Xue, Yan; Cheng, Xiao-Bing; Jiang, Zhi-Hua; Yang, Yi-Chao; Chen, Ying-Dan; Zhou, Xiao-Nong

    2015-12-01

    The nitric oxide (NO) formation and intrinsic nitrosation may be involved in the possible mechanisms of liver fluke-associated carcinogenesis. We still do not know much about the responses of inducible NO synthase (iNOS) induced by Clonorchis sinensis infection. This study was conducted to explore the pathological lesions and iNOS expressions in the liver of mice with different infection intensity levels of C. sinensis. Extensive periductal inflammatory cell infiltration, bile duct hyperplasia, and fibrosis were commonly observed during the infection. The different pathological responses in liver tissues strongly correlated with the infection intensity of C. sinensis. Massive acute spotty necrosis occurred in the liver parenchyma after a severe infection. The iNOS activity in liver tissues increased, and iNOS-expressing cells with morphological differences were observed after a moderate or severe infection. The iNOS-expressing cells in liver tissues had multiple origins.

  3. Microscopic analysis of the chromium content in the chromium-induced malignant and premalignant bronchial lesions of the rat

    International Nuclear Information System (INIS)

    Takahashi, Yuji; Kondo, Kazuya; Ishikawa, Sumiyo; Uchihara, Hiroshi; Fujino, Haruhiko; Sawada, Naruhiko; Miyoshi, Takanori; Sakiyama, Shoji; Izumi, Keisuke; Monden, Yasumasa

    2005-01-01

    Objective: Our previous studies demonstrated that the frequency of gene instability in lung cancer of chromate workers was very high, but the frequencies of the p53 and ras gene mutations were low. To clarify the carcinogenesis of chromate in the lung, we established a chromate-induced cancer model in the rat proximal airway and examined the relationship between chromium accumulations and the chromium-induced cancer and premalignant bronchial lesions of the rat. Methods: Fifteen male, bred, 12-week-old Jcl-Wister rats were used. A pellet of strontium chromate were inserted into the bronchus of the rats. The rats were sacrificed 9 months after the pellet was inserted. We pathologically examined the region of the bronchi to which the pellet was attached. We quantified the amount of chromium accumulation in the bronchial lesions using a microscopic X-ray fluorescence analyzer. Results: Of the 15 rats, 1 rat had a lesion of squamous cell carcinoma (SCC), 7 rats had carcinoma in situ (CIS) or dysplasia, 8 rats had squamous metaplasia, and 5 rats had goblet cell hyperplasia. The amounts of chromium accumulation in normal epithelium (n=24), goblet cell hyperplasia (n=14), squamous metaplasia (n=8), and dysplasia plus CIS plus SCC (n=9) were 500±1354, 713±1062, 941±1328, and 3511±4473 (mean±SD) counts/s/mA, respectively. The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium (Spearman's correlation coefficient by ranks, rs=0.454, P<0.01). Conclusions: The amount of chromium accumulation was significantly increased according to the progression of malignant change of the bronchial epithelium. Examining the genetic alterations of histologic changes in this model was helpful in elucidating the process of carcinogenesis of chromium in the lung

  4. The microRNA effector RNA-induced silencing complex in hidradenitis suppurativa: a significant dysregulation within active inflammatory lesions.

    Science.gov (United States)

    Hessam, S; Sand, M; Skrygan, M; Bechara, Falk G

    2017-09-01

    Recently, we could show that the expression levels of the key regulators of the microRNA (miRNA) maturation and transport were dysregulated in inflamed hidradenitis suppurativa (HS) tissue (Heyam et al. in Wiley Interdiscip Rev RNA 6:271-289, 2015). The RNA-induced silencing complex (RISC) is the central element of the miRNA pathway and regulates miRNA formation and function. We investigated the expression of the RISC components, namely transactivation-responsive RNA-binding protein-1 (TRBP1), TRBP2, protein activator (PACT) of the interferon-induced protein kinase R, Argonaute RISC Catalytic Component-1 (AGO1) and Component-2 (AGO2), metadherin, and staphylococcal nuclease and Tudor domain-containing-1 (SND1) in inflamed HS tissue compared to healthy and psoriatic controls by real-time reverse transcription polymerase chain reaction. Expression levels of all investigated components were significantly lower in lesional HS skin (n = 18) compared to healthy controls (n = 10). TRBP1, PACT, AGO1, AGO2, and SND1 expression levels were significantly down-regulated in lesional HS skin compared to healthy-appearing perilesional skin (n = 7). TRBP2 and SND1 expression levels were significantly lower in healthy-appearing perilesional skin compared to healthy controls. In lesional HS skin, expression levels of PACT, AGO1, and AGO2 were significantly lower compared to psoriatic skin (n = 10). In summary, our data showed that all investigated components of RISC are dysregulated in the skin of HS patients, providing support for the hypothesis that miRNAs may have a pathological role in the inflammatory pathogenesis of HS.

  5. Peripheral facial nerve lesions induce changes in the firing properties of primary motor cortex layer 5 pyramidal cells.

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    Múnera, A; Cuestas, D M; Troncoso, J

    2012-10-25

    Facial nerve lesions elicit long-lasting changes in vibrissal primary motor cortex (M1) muscular representation in rodents. Reorganization of cortical representation has been attributed to potentiation of preexisting horizontal connections coming from neighboring muscle representation. However, changes in layer 5 pyramidal neuron activity induced by facial nerve lesion have not yet been explored. To do so, the effect of irreversible facial nerve injury on electrophysiological properties of layer 5 pyramidal neurons was characterized. Twenty-four adult male Wistar rats were randomly subjected to two experimental treatments: either surgical transection of mandibular and buccal branches of the facial nerve (n=18) or sham surgery (n=6). Unitary and population activity of vibrissal M1 layer 5 pyramidal neurons recorded in vivo under general anesthesia was compared between sham-operated and facial nerve-injured animals. Injured animals were allowed either one (n=6), three (n=6), or five (n=6) weeks recovery before recording in order to characterize the evolution of changes in electrophysiological activity. As compared to control, facial nerve-injured animals displayed the following sustained and significant changes in spontaneous activity: increased basal firing frequency, decreased spike-associated local field oscillation amplitude, and decreased spontaneous theta burst firing frequency. Significant changes in evoked-activity with whisker pad stimulation included: increased short latency population spike amplitude, decreased long latency population oscillations amplitude and frequency, and decreased peak frequency during evoked single-unit burst firing. Taken together, such changes demonstrate that peripheral facial nerve lesions induce robust and sustained changes of layer 5 pyramidal neurons in vibrissal motor cortex. Copyright © 2012 IBRO. Published by Elsevier Ltd. All rights reserved.

  6. The Effect of Different Formulations of Calcium Hydroxide on Healing of Intentionally Induced Periapical Lesions in Dogs

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    Salma El-Ashry, Ashraf Abu-Seida1, Houry Al-Boghdady2, Kareem El-Batouty and Medhat Abdel-Fattah

    2013-01-01

    Full Text Available The aim of the present work is to study the effect of different formulations of Ca (OH2 on healing of induced periapical lesions in dog. A total of 96 teeth with intentionally induced periapical lesions were classified according to the observation period into three groups; I, II and III (2 dogs each. Each group was subdivided into four subgroups (8 teeth each namely; A, B, C and D which were dressed with Ca(OH2 with saline, Ca(OH2 with chlrohexidine, Ca(OH2 with iodoform and control respectively. Histopathological findings showed that the apical and periapical repair were better in subgroup A than in other subgroups in all groups. Total inflammatory cell count was significantly different between the four subgroups in group I. In both groups II and III, there was no significant difference between subgroups B and C. In conclusion, the use of saline as a vehicle for Ca (OH2 has a favorable action on periapical tissue healing in endodontically treated dogs.

  7. High level expression of human epithelial β-defensins (hBD-1, 2 and 3 in papillomavirus induced lesions

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    Chong Kong T

    2006-09-01

    Full Text Available Abstract Background Epithelial defensins including human β-defensins (hBDs and α-defensins (HDs are antimicrobial peptides that play important roles in the mucosal defense system. However, the role of defensins in papillomavirus induced epithelial lesions is unknown. Results Papilloma tissues were prospectively collected from 15 patients with recurrent respiratory papillomatosis (RRP and analyzed for defensins and chemokine IL-8 expression by quantitative, reverse-transcriptase polymerase chain reaction (RT-PCR assays. HBD-1, -2 and -3 mRNAs were detectable in papilloma samples from all RRP patients and the levels were higher than in normal oral mucosal tissues from healthy individuals. Immunohistochemical analysis showed that both hBD-1 and 2 were localized in the upper epithelial layers of papilloma tissues. Expression of hBD-2 and hBD-3 appeared to be correlated as indicated by scatter plot analysis (r = 0.837, p Conclusion Human β-defensins are upregulated in respiratory papillomas. This novel finding suggests that hBDs might contribute to innate and adaptive immune responses targeted against papillomavirus-induced epithelial lesions.

  8. Suppression of neurotoxic lesion-induced seizure activity: evidence for a permanent role for the hippocampus in contextual memory.

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    Fraser T Sparks

    Full Text Available Damage to the hippocampus (HPC using the excitotoxin N-methyl-D-aspartate (NMDA can cause retrograde amnesia for contextual fear memory. This amnesia is typically attributed to loss of cells in the HPC. However, NMDA is also known to cause intense neuronal discharge (seizure activity during the hours that follow its injection. These seizures may have detrimental effects on retrieval of memories. Here we evaluate the possibility that retrograde amnesia is due to NMDA-induced seizure activity or cell damage per se. To assess the effects of NMDA induced activity on contextual memory, we developed a lesion technique that utilizes the neurotoxic effects of NMDA while at the same time suppressing possible associated seizure activity. NMDA and tetrodotoxin (TTX, a sodium channel blocker, are simultaneously infused into the rat HPC, resulting in extensive bilateral damage to the HPC. TTX, co-infused with NMDA, suppresses propagation of seizure activity. Rats received pairings of a novel context with foot shock, after which they received NMDA-induced, TTX+NMDA-induced, or no damage to the HPC at a recent (24 hours or remote (5 weeks time point. After recovery, the rats were placed into the shock context and freezing was scored as an index of fear memory. Rats with an intact HPC exhibited robust memory for the aversive context at both time points, whereas rats that received NMDA or NMDA+TTX lesions showed a significant reduction in learned fear of equal magnitude at both the recent and remote time points. Therefore, it is unlikely that observed retrograde amnesia in contextual fear conditioning are due to disruption of non-HPC networks by propagated seizure activity. Moreover, the memory deficit observed at both time points offers additional evidence supporting the proposition that the HPC has a continuing role in maintaining contextual memories.

  9. [Accident-induced lesions of the facial nerve in relation to the extent of pyramidal pneumatization].

    Science.gov (United States)

    Kadoori, S; Limberg, C

    1985-12-01

    Perilabyrinthine pneumatisation of the petrous pyramid constitutes a risk factor for the facial nerve in its labyrinthine part in a fracture of the temporal bone because serious splintering of bone is possible. Splinters dislocated into the Fallopian canal may damage the nerve seriously. On the other hand a perineural haematoma can flow out of the canal into the neighbouring cells through dehiscences or through the fractured canal walls and a compression of the nerve may be avoided. The decision to undertake early surgical intervention must take into account the degree of pneumatisation of the pyramid in posttraumatic lesions of the facial nerve. The timing and extent of recovery cannot be predicted.

  10. The hypoxic cancer secretome induces pre-metastatic bone lesions through lysyl oxidase

    DEFF Research Database (Denmark)

    Cox, Thomas R; Rumney, Robin M H; Schoof, Erwin M

    2015-01-01

    Tumour metastasis is a complex process involving reciprocal interplay between cancer cells and host stroma at both primary and secondary sites, and is strongly influenced by microenvironmental factors such as hypoxia. Tumour-secreted proteins play a crucial role in these interactions and present...... morbidity and mortality. The molecular interactions governing the early events of osteolytic lesion formation are currently unclear. Here we show hypoxia to be specifically associated with bone relapse in patients with oestrogen-receptor negative breast cancer. Global quantitative analysis of the hypoxic...

  11. Oral lichenoid contact lesions induced by areca nut and betel quid chewing: a mini review.

    Science.gov (United States)

    Reichart, Peter A; Warnakulasuriya, Saman

    2012-08-01

    Betel quid (BQ) and areca nut chewing is widely prevalent in many parts of Asia and Asian-migrant communities throughout the world. Global reports estimate 600 million users. Sufficient evidence of carcinogenicity has been found for BQ and its main ingredient, areca nut. BQ areca nut users have an increased risk of potentially malignant disorders. Among chewers, BQ remains in contact with the oral mucosa for prolonged periods. This review examines the clinical and pathological aspects of lichenoid lesions caused by areca nut and BQ, a condition that has received little attention in the published literature. © 2012 Blackwell Publishing Asia Pty Ltd.

  12. Interaction of DNA-lesions induced by sodium fluoride and radiation and its influence in apoptotic induction in cancer cell lines

    Directory of Open Access Journals (Sweden)

    Santosh Podder

    2015-01-01

    Full Text Available Fluoride is an essential trace element but also an environmental contaminant with major sources of exposure being drinking water, food and pesticides. Previous studies showed that sodium fluoride (NaF at 5 mM or more is required to induce apoptosis and chromosome aberrations and proposed that DNA damage and apoptosis play an important role in toxicity of excessive fluoride. The aim of this study is directed to understand the nature of DNA-lesions induced by NaF by allowing its interaction with radiation induced DNA-lesions. NaF 5 mM was used after observing inability to induce DNA damages and apoptosis by single exposure with 50 μM or 1 mM NaF. Co-exposure to NaF and radiation significantly increased the frequency of aberrant metaphases and exchange aberrations in human lymphocytes and arrested the cells in G1 stage instead of apoptotic death. Flow cytometric analysis, DNA fragmentation and PARP-cleavage analysis clearly indicated that 5 mM NaF together with radiation (1 Gy induced apoptosis in both U87 and K562 cells due to down regulation of expression of anti-apoptotic proteins, like Bcl2 in U87 and inhibitors of apoptotic proteins like survivin and cIAP in K562 cells. This study herein suggested that single exposure with extremely low concentration of NaF unable to induce DNA lesions whereas higher concentration induced DNA lesions interact with the radiation-induced DNA lesions. Both are probably repaired rapidly thus showed increased interactive effect. Coexposure to NaF and radiation induces more apoptosis in cancer cell lines which could be due to increased exchange aberrations through lesions interaction and downregulating anti-apoptotic genes.

  13. Intestinal Lymphangiectasia

    Science.gov (United States)

    ... Overview of Crohn Disease Additional Content Medical News Intestinal Lymphangiectasia (Idiopathic Hypoproteinemia) By Atenodoro R. Ruiz, Jr., MD, ... Overview of Malabsorption Bacterial Overgrowth Syndrome Celiac Disease Intestinal ... Intolerance Short Bowel Syndrome Tropical Sprue Whipple ...

  14. Intestinal Obstruction

    Science.gov (United States)

    ... Colostomy ) is required to relieve an obstruction. Understanding Colostomy In a colostomy, the large intestine (colon) is cut. The part ... 1 What Causes Intestinal Strangulation? Figure 2 Understanding Colostomy Gastrointestinal Emergencies Overview of Gastrointestinal Emergencies Abdominal Abscesses ...

  15. Estrogen protects the liver and intestines against sepsis-induced injury in rats.

    Science.gov (United States)

    Sener, Göksel; Arbak, Serap; Kurtaran, Pelin; Gedik, Nursal; Yeğen, Berrak C

    2005-09-01

    Sepsis is commonly associated with enhanced generation of reactive oxygen metabolites, leading to multiple organ dysfunctions. The aim of this study was to examine the putative protective role of estradiol against sepsis-induced oxidative organ damage. Sepsis was induced by cecal ligation and puncture method in Wistar albino rats. Sham-operated (control) and sepsis groups received saline or estradiol propionate (10 mg/kg) intraperitoneally immediately after the operation and at 12 h. Twenty-four hours after the surgery, rats were decapitated and malondialdehyde, glutathione levels, and myeloperoxidase activity were determined in the liver and ileum, while oxidant-induced tissue fibrosis was determined by collagen contents. Tissues were also examined microscopically. Serum aspartate aminotransferase, alanine aminotransferase levels, and lactate dehydrogenase were measured for the evaluation of liver functions and tissue damage, respectively. Tumor necrosis factor-alpha was also assayed in serum samples. In the saline-treated sepsis group, glutathione levels were decreased significantly, while the malondialdehyde levels, myeloperoxidase activity, and collagen content were increased in the tissues (P Liver function tests and tumor necrosis factor-alpha levels, which were increased significantly (P < 0.001) following sepsis, were decreased (P < 0.05 to P < 0.001) with estradiol treatment. The results demonstrate the role of oxidative mechanisms in sepsis-induced tissue damage, and estradiol, by its antioxidant properties, ameliorates oxidative organ injury, implicating that treatment with estrogens might be applicable in clinical situations to ameliorate multiple organ damage induced by sepsis.

  16. Osteopontin mediates Citrobacter rodentium-induced colonic epithelial cell hyperplasia and attaching-effacing lesions.

    Science.gov (United States)

    Wine, Eytan; Shen-Tu, Grace; Gareau, Mélanie G; Goldberg, Harvey A; Licht, Christoph; Ngan, Bo-Yee; Sorensen, Esben S; Greenaway, James; Sodek, Jaro; Zohar, Ron; Sherman, Philip M

    2010-09-01

    Although osteopontin (OPN) is up-regulated in inflammatory bowel diseases, its role in disease pathogenesis remains controversial. The objective of this study was to determine the role of OPN in host responses to a non-invasive bacterial pathogen, Citrobacter rodentium, which serves as a murine infectious model of colitis. OPN gene knockout and wild-type mice were infected orogastrically with either C. rodentium or Luria-Bertani (LB) broth. Mouse-derived OPN(+/+) and OPN(-/-) fibroblasts were incubated with C. rodentium and attaching-effacing lesions were demonstrated using transmission electron microscopy and immunofluorescence. Colonic expression of OPN was increased by C. rodentium infection of wild-type mice. Furthermore, colonic epithelial cell hyperplasia, the hallmark of C. rodentium infection, was reduced in OPN(-/-) mice, and spleen enlargement by infection was absent in OPN(-/-) mice. Rectal administration of OPN to OPN(-/-) mice restored these effects. There was an 8- to 17-fold reduction in bacterial colonization in OPN(-/-) mice, compared with wild-type mice, which was accompanied by reduced attaching-effacing lesions, both in infected OPN(-/-) mice and OPN(-/-) mouse fibroblasts. Moreover, adhesion pedestals were restored in OPN(-/-) cells complemented with human OPN. Therefore, lack of OPN results in decreased pedestal formation, colonization, and colonic epithelial cell hyperplasia responses to C. rodentium infection, indicating that OPN impacts disease pathogenesis through bacterial attachment and altered host immune responses.

  17. Activated Α7nachr Improves Postoperative Cognitive Dysfunction and Intestinal Injury Induced by Cardiopulmonary Bypass in Rats: Inhibition of the Proinflammatory Response Through the Th17 Immune Response

    Directory of Open Access Journals (Sweden)

    Keyan Chen

    2018-04-01

    Full Text Available Backgrund/Aims: To investigate the effects of activated α7 nicotinic acetylcholine receptor (α7nAChR on postoperative cognitive dysfunction (POCD and intestinal injury induced by cardiopulmonary bypass (CPB and its relationship with the Th17 response in order to provide a theoretical basis for organ protection and targeted drug therapy during the perioperative period. Methods: Sprague-Dawley rat models of CPB were established. Rat intestinal and brain injuries were observed after CPB using hematoxylin and eosin staining. Cell apoptosis was determined using terminal deoxynucleotidyl transferase dUTP nick end labeling. Inflammatory factors and markers of brain injury in rat serum were measured using enzyme-linked immunosorbent assay. The expression levels of Bcl-2, Bax, caspase-3, ZO-1, occludin, AQP4, RORγT, and α7nAchR were examined using western blotting. Transcription factor RORγT expression was determined using real-time fluorescent quantitative polymerase chain reaction. Th17 cells in the peripheral blood and spleen were determined using flow cytometry. α7nAchR knockout rats were established. The Th17 response in the peripheral blood and spleen of α7nAchR knockout rats was further verified using flow cytometry. Results: CPB can induce POCD and intestinal injury in rats. α7nAchR activation markedly reduced intestinal injury, POCD, neuronal apoptosis, proinflammatory factor expression, and number of CD4+IL-17+ cells. α7nAchR knockout significantly increased serum D-lactic acid, FABP2, S-100β, NSE, TNF-α, IL-6, and IL-17 secretion. The number of CD4+IL-17+ cells was also significantly increased. Conclusion: α7nAchR activation markedly ameliorates the intestinal injury and POCD induced by CPB. Inhibition of the Th17 immune response can reduce the proinflammatory response, which could provide a new method for clinical perioperative organ protection and targeted drug therapy.

  18. An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse.

    Science.gov (United States)

    Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A; Borrelli, Francesca

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for "CBD botanical drug substance," on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was evaluated in the experimental model of intestinal hypermotility induced by irritant croton oil. CBD BDS or pure CBD were given - either intraperitoneally or by oral gavage - after the inflammatory insult (curative protocol). The amounts of CBD in the colon, brain, and liver after the oral treatments were measured by high-performance liquid chromatography coupled to ion trap-time of flight mass spectrometry. CBD BDS, both when given intraperitoneally and by oral gavage, decreased the extent of the damage (as revealed by the decrease in the colon weight/length ratio and myeloperoxidase activity) in the DNBS model of colitis. It also reduced intestinal hypermotility (at doses lower than those required to affect transit in healthy mice) in the croton oil model of intestinal hypermotility. Under the same experimental conditions, pure CBD did not ameliorate colitis while it normalized croton oil-induced hypermotility when given intraperitoneally (in a dose-related fashion) or orally (only at one dose). In conclusion, CBD BDS, given after the inflammatory insult, attenuates injury and motility in intestinal models of inflammation. These findings sustain the rationale of combining CBD with other minor Cannabis constituents and support the clinical development of CBD BDS for IBD treatment.

  19. Curcuminoids from Curcuma longaL. reduced intestinal mucositis induced by 5-fluorouracil in mice: Bioadhesive, proliferative, anti-inflammatory and antioxidant effects

    Directory of Open Access Journals (Sweden)

    Edvande Xavier dos Santos Filho

    Full Text Available Introduction: Intestinal mucositis is a frequent limiting factor in anticancer therapy and there is currently no broadly effective treatment targeted to cure this side effect. Objective: This study aimed to evaluate the effects of a mucoadhesive formulation containing curcuminoids (MFC from Curcuma longa L. on the pathogenesis of 5-fluorouracil (5-FU-induced intestinal mucositis. Methods: Three intraperitoneal 5-FU injections (200 mg/kg were used to induce intestinal mucositis in adult Swiss male mice. Treatment was provided orally (MFC 3.75, 7.5 and 15 mg/kg, thirty minutes before 5-FU injections, daily until euthanasia. Duodenal samples were collected to perform morphometric and histopathological analysis, to investigate the expression of Ki-67, p53, Bax and Bcl-2 by immunohistochemistry, to evaluate neutrophil activity myeloperoxidase (MPO-mediated and oxidative stress by malondialdehyde (MDA determination. Mice body weight was assessed as well. Results: As expected, 5-FU induced a significant weight loss (∼17%, P < 0.001, shortening in villi height (∼55.4% and crypts depth (∼47%, and increased (∼64% the histological severity score when compared to other groups (P < 0.05. These pathological changes were markedly alleviated by the three MFC treatment doses (P < 0.05, in special with the dose MFC 15 mg/kg. This dose also stimulated cell proliferation by ∼90% in the epithelial cells lining from villi and crypts (P < 0.05, reduced MPO levels and MDA formation by 60% and 44%, respectively (P < 0.05. Conclusions: Our data suggest the therapeutic potential of the formulation for treating intestinal mucositis in mice. Supplementary studies are underway searching for the elucidation of mechanisms involved in the protective effects of MFC in order to make this formulation a clinical tool for mucositis treatment. Keywords: Mucoadhesive formulation, Curcuminoids, Curcuma longa L, Intestinal mucositis, 5-Fluorouracil

  20. Modulation of pathogen-induced CCL20 secretion from HT-29 human intestinal epithelial cells by commensal bacteria.

    LENUS (Irish Health Repository)

    Sibartie, Shomik

    2009-01-01

    BACKGROUND: Human intestinal epithelial cells (IECs) secrete the chemokine CCL20 in response to infection by various enteropathogenic bacteria or exposure to bacterial flagellin. CCL20 recruits immature dendritic cells and lymphocytes to target sites. Here we investigated IEC responses to various pathogenic and commensal bacteria as well as the modulatory effects of commensal bacteria on pathogen-induced CCL20 secretion. HT-29 human IECs were incubated with commensal bacteria (Bifidobacterium infantis or Lactobacillus salivarius), or with Salmonella typhimurium, its flagellin, Clostridium difficile, Mycobacterium paratuberculosis, or Mycobacterium smegmatis for varying times. In some studies, HT-29 cells were pre-treated with a commensal strain for 2 hr prior to infection or flagellin stimulation. CCL20 and interleukin (IL)-8 secretion and nuclear factor (NF)-kappaB activation were measured using enzyme-linked immunosorbent assays. RESULTS: Compared to untreated cells, S. typhimurium, C. difficile, M. paratuberculosis, and flagellin activated NF-kappaB and stimulated significant secretion of CCL20 and IL-8 by HT-29 cells. Conversely, B. infantis, L. salivarius or M. smegmatis did not activate NF-kappaB or augment CCL20 or IL-8 production. Treatment with B. infantis, but not L. salivarius, dose-dependently inhibited the baseline secretion of CCL20. In cells pre-treated with B. infantis, C. difficile-, S. typhimurium-, and flagellin-induced CCL20 were significantly attenuated. B. infantis did not limit M. Paratuberculosis-induced CCL20 secretion. CONCLUSION: This study is the first to demonstrate that a commensal strain can attenuate CCL20 secretion in HT-29 IECs. Collectively, the data indicate that M. paratuberculosis may mediate mucosal damage and that B. infantis can exert immunomodulatory effects on IECs that mediate host responses to flagellin and flagellated enteric pathogens.

  1. Saponin-containing subfractions of soybean molasses induce enteritis in the distal intestine of Atlantic salmon

    NARCIS (Netherlands)

    Knudsen, D.; Urán, P.; Arnous, A.; Koppe, W.

    2007-01-01

    The current work aimed at tracing the causative components for soybean-induced enteritis in Atlantic salmon (Salmo salar L.). Soybean molasses was subjected to phase separation using n-butanol. Three subfractions were obtained as follows: butanol phase, precipitate, and water phase. The biochemical

  2. Vagal afferents are essential for maximal resection-induced intestinal adaptive growth in orally fed rats

    DEFF Research Database (Denmark)

    Nelson, David W; Liu, Xiaowen; Holst, Jens Juul

    2006-01-01

    in mucosal mass, protein, DNA, and histology. Both systemic and perivagal capsaicin significantly attenuated by 48-100% resection-induced increases in ileal mucosal mass, protein, and DNA in rats fed orally. Villus height was significantly reduced in resected rats given capsaicin compared with vehicle...

  3. Evidence for the involvement of 5-lipoxygenase products in ethanol-induced intestinal plasma protein loss

    International Nuclear Information System (INIS)

    Beck, I.T.; Boyd, A.J.; Dinda, P.K.

    1988-01-01

    In this study the authors investigated whether the products of 5-lipoxygenase (5-LO) were involved in the jejunal microvascular injury induced by intraluminal ethanol (ETH). A group of rabbits was given orally a selective inhibitor of 5-LO in two 10-mg doses, 24, and 2 h before the experiments. A jejunal segment was perfused with a control solution (control segment) and an adjacent segment with an ETH-containing solution (ETH-perfused segment). In a series of experiments, they measured 5-LO activity of the jejunal segments of both groups using the generation of leukotriene B 4 (LTB 4 ) as an index. In a second series of experiments, they determined the ETH-induced intraluminal protein loss, which was taken as a measure of mucosal microvascular damage. The ETH-induced increase in protein loss was significantly lower in the treated than in the untreated group. These findings suggest that products of 5-LO are involved in the ETH-induced jejunal microvascular injury

  4. Sodium butyrate attenuates soybean oil-based lipid emulsion-induced increase in intestinal permeability of lipopolysaccharide by modulation of P-glycoprotein in Caco-2 cells

    International Nuclear Information System (INIS)

    Yan, Jun-Kai; Gong, Zi-Zhen; Zhang, Tian; Cai, Wei

    2017-01-01

    Down-regulation of intestinal P-glycoprotein (P-gp) by soybean oil-based lipid emulsion (SOLE) may cause elevated intestinal permeability of lipopolysaccharide (LPS) in patients with total parenteral nutrition, but the appropriate preventative treatment is currently limited. Recently, sodium butyrate (NaBut) has been demonstrated to regulate the expression of P-gp. Therefore, this study aimed to address whether treatment with NaBut could attenuate SOLE-induced increase in intestinal permeability of LPS by modulation of P-gp in vitro. Caco-2 cells were exposed to SOLE with or without NaBut. SOLE-induced down-regulation of P-gp was significantly attenuated by co-incubation with NaBut. Nuclear recruitment of FOXO 3a in response to NaBut was involved in P-gp regulation. Transport studies revealed that SOLE-induced increase in permeability of LPS was significantly attenuated by co-incubation with NaBut. Collectively, our results suggested that NaBut may be a potentially useful medication to prevent SOLE-induced increase in intestinal permeability of LPS. - Highlights: • Caco-2 cells were used as models for studying parenteral nutrition in vitro. • NaBut restored SOLE-induced down-regulation of P-gp in Caco-2 cells. • Regulation of P-gp by NaBut was mediated via nuclear recruitment of FOXO 3a. • NaBut modulated the permeability of LPS by P-gp function, not barrier function.

  5. Attenuation of stress-induced gastric lesions by lansoprazole, PD-136450 and ranitidine in rats.

    Science.gov (United States)

    Chandranath, S I; Bastaki, S M A; D'Souza, A; Adem, A; Singh, J

    2011-03-01

    Combining restraint with cold temperature (4°C) consistently induces gastric ulceration in rats after 3.5 h. The cold restraint-stress (CRS) method provides a suitable model for acute ulcer investigations. This study compares the antiulcer activities of lansoprazole (a proton pump inhibitor), PD-136450 (CCK(2)/gastrin receptor antagonist) and ranitidine (histamine H(2) receptor antagonist) on CRS-induced gastric ulcers in rats. The results have shown that lansoprazole, which is a potent anti-secretory agent, provides complete protection in this model of ulcer formation. The use of indomethacin pretreatment to inhibit the prostaglandin (PG) synthesis and N(G)-nitro L-arginine methyl ester (L-NAME) pretreatment to inhibit nitric oxide synthase did not alter the lansoprazole-induced inhibition of ulcer index obtained in the untreated Wistar rats indicating that these two systems were not involved in the activation of lansoprazole. PD-136450, an effective anti-secretory agent against gastrin- but not dimaprit-induced stimulation, evoked a dose-dependent inhibition of CRS-induced gastric ulcers. The results show that both PG and nitric oxide pathways can influence the inhibitory effect of PD-136450 against CRS-induced gastric ulcer. The antiulcer activities of both lansoprazole and PD-136450 were compared to that of ranitidine. The results showed that ranitidine was more potent than lansoprazole and PD-136450 in inhibiting CRS-induced gastric ulcers and its effect was shown to be influenced by PG as well as nitric oxide synthase. The results of this study have demonstrated that although lansoprazole, PD-136450 and ranitidine were protective against CRS-induced gastric ulcers, the antiulcer activities of PD-136450 and ranitidine involved both PG and nitric oxide pathways, while lansoprazole acted independently of these two systems during CRS.

  6. Topical chlorophyll-pheophytin derivative-mediated photodynamic therapy for DMBA-induced hamster buccal pouch premaligant lesions: an in vivo study

    Science.gov (United States)

    Hsu, Yih-Chih; Chiang, Chung-Pin; Chen, Jian Wen; Lee, Jeng-Woei; How, Mon-Hsin

    2010-02-01

    In Taiwan, oral cancer has become a prominent cancer because of its highest annual increase rate among all cancer diseases. Betel quid chewing habit is a major risk factor for oral precancerous and cancerous lesions and there are more than two million people who have this habit in Taiwan. Our previous studies showed that chlorophyll-pheophytin derivative (CPD)-mediated PDT is very effective for killing of SCC-4 cell lines in vitro. In order to decrease the systemic phototoxic effect of CPD, this study was designed to use a topical CPD-mediated PDT for treatment of DMBA-induced hamster buccal pouch precancerous lesions. DMBA was applied to one of the buccal pouches of hamsters thrice a week for 8 to 10 weeks. Precancerous lesions of moderate to severe dysplasia were induced and proven by histological examination. These induced precancerous lesions were used for testing the efficacy of topical CPD-mediated PDT. Before PDT, fluorescence spectroscopy was used to determine when CPD reached its peak level in the lesional epithelial cells after topical application of CPD gel. We found that CPD reached its peak level in precancerous lesions about 1 hour (range, 0 to 30 hours) after topical application of CPD gel. The precancerous lesions in hamsters were then treated with topical CPD-mediated PDT (fluence rate: 200 mW/cm2; light exposure dose 100 J/cm2) using the portable WonderLight LED 635 nm fiber-guided light device once or twice a week. Visual and histological examination demonstrated that topical CPD-mediated PDT was partially effective treatment modality for DMBA-induced hamster buccal pouch precancerous lesions.

  7. Increased oral AUC of baicalin in streptozotocin-induced diabetic rats due to the increased activity of intestinal beta-glucuronidase.

    Science.gov (United States)

    Liu, Li; Deng, Yuan-Xiong; Liang, Yan; Pang, Xiao-Yan; Liu, Xiao-Dong; Liu, Yao-Wu; Yang, Jian-Song; Xie, Lin; Wang, Guang-Ji

    2010-01-01

    The purpose of the study was to investigate the pharmacokinetics of baicalin, a major bioactive component of Scutellariae radix, in diabetic conditions. The 4-week diabetic rats were induced by intraperitoneal administration of streptozotocin. Plasma concentrations of baicalin were measured following oral (200 mg/kg) or intravenous (12 mg/kg) administration. Everted intestinal transport, intestinal mucosal metabolism of baicalin and intestinal beta-glucuronidase activity were also investigated. It was found that the diabetic condition significantly increased the exposure of baicalin following oral doses (AUC 100.77 +/- 4.16 microg x h/mL in diabetic rats vs. 48.48 +/- 7.94 microg x h/mL in normal rats). In contrast, the diabetic condition significantly decreased the exposure of baicalin following intravenous doses (AUC 11.20 +/- 2.28 microg x h/mL in diabetic rats vs. 18.02 +/- 3.45 microg x h/mL in normal rats). We also found lower apparent permeability coefficients of baicalin in the ileum of diabetic rats (8.43 x 10 (-6) +/- 2.40 x 10 (-6) cm/s in diabetic rats vs. 5.21 x 10 (-5) +/- 1.55 x 10 (-5) cm/s in normal rats). Further studies showed that the diabetic condition enhanced the hydrolysis of baicalin to baicalein in intestinal mucosal, accompanied by an increase of beta-glucuronidase activity. All these results suggested that the higher oral exposure of baicalin in diabetic rats did not result from the decreased hepatic metabolism or increased intestinal absorption of baicalin. The enhancement of intestinal beta-glucuronidase activity may partly account for the higher exposure of baicalin in diabetic rats after oral administration. Copyright Georg Thieme Verlag KG Stuttgart . New York.

  8. The intestinotrophic peptide, glp-2, counteracts intestinal atrophy in mice induced by the epidermal growth factor receptor inhibitor, gefitinib

    DEFF Research Database (Denmark)

    Hare, Kristine Juul; Hartmann, Bolette; Kissow, Hannelouise

    2007-01-01

    of the segments of the gastrointestinal tract were determined, and histologic sections were analyzed by morphometric methods. RESULTS: A significant atrophy of the small-intestinal wall was observed after treatment with gefitinib because both intestinal weight and morphometrically estimated villus height...

  9. Low-methoxyl lemon pectin attenuates inflammatory responses and improves intestinal barrier integrity in caerulein-induced experimental acute pancreatitis

    NARCIS (Netherlands)

    Sun, Yajun; He, Yue; Wang, Fei; Zhang, Hao; de Vos, Paul; Sun, Jia

    Scope: Acute pancreatitis (AP) is a common clinical acute abdominal disease. The intestinal injury associated with AP will aggravate the condition retroactively. This study investigates whether the low-methoxyl pectin (LMP) isolated from lemon could attenuate AP and associated intestinal injury.

  10. The effects of herbs on the radiation-induced apoptosis in intestinal crypt cells

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Sung Ho; An, Mi Ra; Nah, Seung Yeol; Lee, Jong Hwan; Kim, Jae Ha; Shin, Dong Ho [Chonnam National Univ., Gwangju (Korea, Republic of); Jo, Sung Kee [KAERI, Daejeon (Korea, Republic of); Jang, Jong Sik [Sangju National Univ., Sangju (Korea, Republic of)

    2001-03-15

    This study was performed to determine the effect of several herbs on radiation-induced apoptosis in jejunal crypt cells. Longyanrou(Euphoris logana), Suanzaoren(Zizyphus vulgaris), Yuanzhi(Polygala tenuifolia), Rensan(Panax ginseng), Fuling(Poria cocos), Muxiang(Saussurea lappa), Chuanxiong(Cnidium offcinale), Baishaoyao(Paeonia lactifolia), Shengma(Cimicifuga heracleifolia), Chaihu(Bupleurum falcatum) and Dongchongxiacao(Paecilomyces japonica) reduced the frequency of radiation-induced apoptosis(p<0.05). Although the mechanisms of this effect remain to be elucidated, these results indicated that Longyanrou, Suanzaoren, Yuanzhi, Rensan, Fuling, Muxiang, Chuanxiong, Baishaoyao, Shengma, Chaihu and Dongchongxiacao might be useful inhibitors of apoptosis, especially since these are relative nontoxic natural products.

  11. Sucralfate protects intestinal epithelial cells from radiation-induced apoptosis in rats

    International Nuclear Information System (INIS)

    Matsuu-Matsuyama, Mutsumi; Shichijo, Kazuko; Okaichi, Kumio

    2006-01-01

    Radiotherapy for malignant pelvic disease is often followed by acute radiation colitis (ARC). It has been reported that sucralfate treatment has a protective effect against ARC, though the mechanisms of action are unknown. The effects of sucralfate on X-ray radiation-induced apoptosis was studied at 4 Gy in the colonic crypt cells of rats. Sucralfate enemas given prior to radiation resulted in the following: reduction in number of apoptotic colonic crypt cells; reduction in number of caspase-3 positive cells; decreases in p53 accumulation and p21 expression; decreases of Bax/Bcl-2 ratio. The protective effects of sucralfate against ARC may be partially due to the suppression of radiation-induced apoptosis by way of p53 in the colon and the protection of the colonic epithelial stem cell region. (author)

  12. Intestinal Dysbiosis and Biotin Deprivation Induce Alopecia through Overgrowth of Lactobacillus murinus in Mice.

    Science.gov (United States)

    Hayashi, Atsushi; Mikami, Yohei; Miyamoto, Kentaro; Kamada, Nobuhiko; Sato, Toshiro; Mizuno, Shinta; Naganuma, Makoto; Teratani, Toshiaki; Aoki, Ryo; Fukuda, Shinji; Suda, Wataru; Hattori, Masahira; Amagai, Masayuki; Ohyama, Manabu; Kanai, Takanori

    2017-08-15

    Metabolism by the gut microbiota affects host physiology beyond the gastrointestinal tract. Here, we find that antibiotic-induced dysbiosis, in particular, overgrowth of Lactobacillus murinus (L. murinus), impaired gut metabolic function and led to the development of alopecia. While deprivation of dietary biotin per se did not affect skin physiology, its simultaneous treatment with vancomycin resulted in hair loss in specific pathogen-free (SPF) mice. Vancomycin treatment induced the accumulation of L. murinus in the gut, which consumes residual biotin and depletes available biotin in the gut. Consistently, L. murinus induced alopecia when monocolonized in germ-free mice fed a biotin-deficient diet. Supplementation of biotin can reverse established alopecia symptoms in the SPF condition, indicating that L. murinus plays a central role in the induction of hair loss via a biotin-dependent manner. Collectively, our results indicate that luminal metabolic alterations associated with gut dysbiosis and dietary modifications can compromise skin physiology. Copyright © 2017. Published by Elsevier Inc.

  13. The frog vestibular system as a model for lesion-induced plasticity: basic neural principles and implications for posture control

    Directory of Open Access Journals (Sweden)

    Francois M Lambert

    2012-04-01

    Full Text Available Studies of behavioral consequences after unilateral labyrinthectomy have a long tradition in the quest of determining rules and limitations of the CNS to exert plastic changes that assist the recuperation from the loss of sensory inputs. Frogs were among the first animal models to illustrate general principles of regenerative capacity and reorganizational neural flexibility after a vestibular lesion. The continuous successful use of the latter animals is in part based on the easy access and identifiability of nerve branches to inner ear organs for surgical intervention, the possibility to employ whole brain preparations for in vitro studies and the limited degree of freedom of postural reflexes for quantification of behavioral impairments and subsequent improvements. Major discoveries that increased the knowledge of post-lesional reactive mechanisms in the central nervous system include alterations in vestibular commissural signal processing and activation of cooperative changes in excitatory and inhibitory inputs to disfacilitated neurons. Moreover, the observed increase of synaptic efficacy in propriospinal circuits illustrates the importance of limb proprioceptive inputs for postural recovery. Accumulated evidence suggests that the lesion-induced neural plasticity is not a goal-directed process that aims towards a meaningful restoration of vestibular reflexes but rather attempts a survival of those neurons that have lost their excitatory inputs. Accordingly, the reaction mechanism causes an improvement of some components but also a deterioration of other aspects as seen by spatio-temporally inappropriate vestibulo-motor responses, similar to the consequences of plasticity processes in various sensory systems and species. The generality of the findings indicate that frogs continue to form a highly amenable vertebrate model system for exploring molecular and physiological events during cellular and network reorganization after a loss of

  14. Effect of dietary fiber on the activity of intestinal and fecal beta-glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis.

    Science.gov (United States)

    Manoj, G; Thampi, B S; Leelamma, S; Menon, P V

    2001-01-01

    The effects of fiber isolated from black gram (Phaseolus mungo) and coconut (Cocos nucifera) kernel on the metabolic activity of intestinal and fecal beta glucuronidase activity during 1,2-dimethylhydrazine induced colon carcinogenesis were studied. The results indicated that the inclusion of fiber from black gram and coconut kernel generally supported lower specific activities and less fecal output of beta-glucuronidase than did the fiber free diet. This study suggests that the fibers isolated from coconut or black gram may potentially play a role in preventing the formation of colon tumors induced by the carcinogen 1,2-dimethylhydrazine by reducing the activity of the intestinal as well as fecal beta-glucuronidase.

  15. Cloning of radiation-induced new gene RS1 expressed in mouse intestinal epithelium by enhanced RACE

    International Nuclear Information System (INIS)

    Wang Fengchao; Wang Junping; Su Yongping; Gao Jinsheng; Lou Shufen; Liu Xiaohong; Ren Jiong; Zhang Bo

    2003-01-01

    Objective: To obtain full-length cDNA of radiation-induced new gene RS1 expressed in mouse intestinal epithelium. Methods: The tissue expression profile of RS1 was analyzed by semi-quantitative RT-PCR to find the target tissue which highly expresses RS1. The total RNA extracted from the corresponding tissue was taken as the template for reverse-transcription. Enhanced RACE PCR was used to clone the full-length cDNA of RS1, including enrichment of the target gene through biotin-labeled probe for magnetic bead purification and nested PCR. Results: About a 2 kb long 3' end was successfully cloned and cloning of the 5' end proceeded well. Conclusion: The result is consistent with our experiment design. The set of combined techniques has been identified with the cloning of full-length cDNA from EST sequence especially when the optimal gene-specific primers are not available or the expression level of target gene is low

  16. Intestinal actinomycosis: a case report

    International Nuclear Information System (INIS)

    Loureiro, C.M.; Labrunie, E.; Pannaim, V.L.N.; Santos, A.A.S. dos; Pereira, A.A.

    1989-01-01

    Intestinal actinomycosis: a case report. The authors describe a case of intestinal actinomycosis, which was manisfestated by abdominal mass and suggested, clinical and radiologically, a bowel carcinoma. They discuss the pathogenesis, and the clinical and radiological manisfestations of this disease, and its differential diagnosis. This is an infrequent disease which must be considered whenever suggestive clinical aspects are associated with a radiological ''malignant pattern'' of a bowel lesion. (author) [pt

  17. The effects of area postrema lesions and selective vagotomy on motion-induced conditioned taste aversion

    Science.gov (United States)

    Fox, Robert A.; Sutton, R. L.; Mckenna, Susan

    1991-01-01

    Conditioned taste aversion (CTA) is one of several behaviors which was suggested as a putative measure of motion sickness in rats. A review is made of studies which used surgical disruption of area postrema or the vagus nerve to investigate whether CTA and vomiting induced by motion may depend on common neural pathways or structures. When the chemoreceptive function of the area postrema (AP) is destroyed by complete ablation, rats develop CTA and cats and monkeys develop CTA and vomit. Thus the AP is not crucially involved in either CTA or vomiting induced by motion. However, after complete denervation of the stomach or after labyrinthectomy rats do not develop CTA when motion is used as the unconditioned stimulus. Studies of brainstem projections of the vagus nerve, the area postrema, the periaqueductal grey, and the vestibular system are used as the basis for speculation about regions which could mediate both motion-induced vomiting and behavioral food aversion.

  18. Percutaneous CT-guided high frequency induced thermotherapy as a treatment hepatocellular carcinoma and hepatic metastatic lesions

    International Nuclear Information System (INIS)

    Lu Ligong; Luo Pengfei; Chen Xiaoming

    2004-01-01

    Objective: To analyze the efficacy, side effects and complications of percutaneous high frequency induced thermotherapy (HiTT) performed under CT guidance involving 36 patients with hepatocellular carcinomas (HCC) and hepatic metastatic lesions. Methods: HiTT was performed in treatment of 36 patients (24 men and 12 women) with 42 hepatocellular carcinoma and hepatic metastatic carcinoma (six patient out of 36 had two nidi). The diameter of the tumors ranged from 1.6 to 7.8 cm (mean, 3.2 cm). The efficacy of HiTT was evaluated with triphasic spiral CT performed 1 month after the procedure. Results: The post-treatment CT scan showed complete necrosis in 33 nidi (78%) out of 42 nidi of hepatocellular carcinoma and hepatic metastatic carcinoma in 30 patients out of 36. Complete necrosis was obtained in 18 (95%) of 19 tumors no larger than 3 cm in diameter, 13 (72%) of 18 tumors between 3.0 and 5.0 cm in diameter. Eleven tumors showed incomplete necrosis. In our study, none of the patients experienced severe complications. All the patients are alive in the follow-up ranging from 2 to 12 months (mean, 7 months). Conclusion: Our research suggests that HiTT can be a safe and effective treatment of hepatocellular carcinomas and hepatic metastatic carcinoma when the lesion is no larger than 3 cm. The treatment is relatively effective for hepatocellular carcinoma between 3 and 5 cm in size. (authors)

  19. Effect of nuclear factor kappa B on intercellular adhesion molecule-1 expression and neutrophil infiltration in lung injury induced by intestinal ischemia/reperfusion in rats

    Science.gov (United States)

    Tian, Xiao-Feng; Yao, Ji-Hong; Li, Ying-Hua; Zhang, Xue-Song; Feng, Bing-An; Yang, Chun-Ming; Zheng, Shu-Sen

    2006-01-01

    AIM: To investigate the role of nuclear factor kappa B (NF-κB) in the pathogenesis of lung injury induced by intestinal ischemia/reperfusion (I/R), and its effect on intercellular adhesion molecule-1 (ICAM-1) expression and neutrophil infiltration. METHODS: Twenty-four Wistar rats were divided randomly into control, I/R and pyrrolidine dithiocarbamate (PDTC) treatment groups, n = 8 in each. I/R group and PDTC treatment group received superior mysenteric artery (SMA) occluding for 1 h and reperfusion for 2 h. PDTC group was administrated with intraperitoneal injection of 2% 100 mg/kg PDTC 1 h before surgery. Lung histology and bronchia alveolus lung fluid (BALF) protein were assayed. Serum IL-6, lung malondialdehyde (MDA) and myeloperoxidase (MPO) as well as the expression level of NF-κB and ICAM-1 were measured. RESULTS: Lung injury induced by intestinal I/R, was characterized by edema, hemorrhage and neutrophil infiltration as well as by the significant rising of BALF protein. Compared to control group, the levels of serum IL-6 and lung MDA and MPO increased significantly in I/R group (P = 0.001). Strong positive expression of NF-κB p65 and ICAM-1 was observed. After the administration of PDTC, the level of serum IL-6, lung MDA and MPO as well as NF-κB and ICAM-1 decreased significantly (P < 0.05) when compared to I/R group. CONCLUSION: The activation of NF-κB plays an important role in the pathogenesis of lung injury induced by intestinal I/R through upregulating the neutrophil infiltration and lung ICAM-1 expression. PDTC as an inhibitor of NF-κB can prevent lung injury induced by intestinal I/R through inhibiting the activity of NF-κB. PMID:16489637

  20. An Orally Active Cannabis Extract with High Content in Cannabidiol attenuates Chemically-induced Intestinal Inflammation and Hypermotility in the Mouse

    OpenAIRE

    Pagano, Ester; Capasso, Raffaele; Piscitelli, Fabiana; Romano, Barbara; Parisi, Olga A.; Finizio, Stefania; Lauritano, Anna; Marzo, Vincenzo Di; Izzo, Angelo A.; Borrelli, Francesca

    2016-01-01

    Anecdotal and scientific evidence suggests that Cannabis use may be beneficial in inflammatory bowel disease (IBD) patients. Here, we have investigated the effect of a standardized Cannabis sativa extract with high content of cannabidiol (CBD), here named CBD BDS for “CBD botanical drug substance,” on mucosal inflammation and hypermotility in mouse models of intestinal inflammation. Colitis was induced in mice by intracolonic administration of dinitrobenzenesulfonic acid (DNBS). Motility was ...

  1. Cytomegalovirus-induced colonic stricture presenting as acute intestinal obstruction in an immunocompetent adult.

    Science.gov (United States)

    Dinesh, B V; Selvaraju, Karthikeyan; Kumar, Sampath; Thota, Sumath

    2013-09-10

    Cytomegalovirus (CMV) infection causes significant morbidty and mortality in immunopromised patients. Though it is usually silent in immunocompetent adults, rarely it can cause serious life-threatening complications. Gastrointestinal tract is one of the commonly involved organs, where it produces a spectrum of clinical manifestation ranging from mild non-specific abdominal pain and diarrhoea to severe infection with toxic megacolon and death. We present a 65-year-old immunocompetent male patient admitted with acute colonic obstruction secondary to CMV-induced colonic stricture, highlighting the importance of considering it as a differential diagnosis for colonic obstruction and reviewing its management.

  2. Vasoactive intestinal peptide causes marked cephalic vasodilation, but does not induce migraine

    DEFF Research Database (Denmark)

    Rahmann, A.; Wienecke, T.; Hansen, J.M.

    2008-01-01

    -blind crossover study. Headache was scored on a verbal rating scale (VRS), mean blood flow velocity in the middle cerebral artery (V-mean MCA) was measured by transcranial Doppler ultrasonography, and diameter of the superficial temporal artery (STA) by high-frequency ultrasound. None of the subjects reported...... a migraine attack after VIP infusion. VIP induced a mild immediate headache (maximum 2 on VRS) compared with placebo (P = 0.005). Three patients reported delayed headache (3-11 h after infusion) after VIP and two after placebo (P = 0.89). V-mean MCA decreased (16.3 +/- 5.9%) and diameter of STA increased...

  3. Effects of Lactobacillus salivarius Ren on cancer prevention and intestinal microbiota in 1, 2-dimethylhydrazine-induced rat model.

    Science.gov (United States)

    Zhang, Ming; Fan, Xing; Fang, Bing; Zhu, Chengzhen; Zhu, Jun; Ren, Fazheng

    2015-06-01

    Probiotics have been suggested as a prophylactic measure in colon cancer. The aim of this study was to investigate the impact of Lactobacillus salivarius Ren (Ren) in modulating colonic microbiota structure and colon cancer incidence in a rat model after injection with 1,2-dimethyl hydrazine (DMH). The results indicated that oral administration of Ren could effectively suppress DMH-induced colonic carcinogenesis. A significant decrease in cancer incidence (87.5% to 25%) was detected in rats fed with a dose of 5 × 10(10) CFU/kg bodyweight per day. Using denaturing gradient gel electrophoresis and Real-time PCR combined with multivariate statistical methods, we demonstrated that injection with DMH significantly altered the rat gut microbiota, while Ren counteracted these DMH-induced adverse effects and promoted reversion of the gut microbiota close to the healthy state. Tvalue biplots followed by band sequencing identified 21 bacterial strains as critical variables affected by DMH and Ren. Injection of DMH significantly increased the amount of Ruminococcus species (sp.) and Clostridiales bacteria, as well as decreasing the Prevotella sp. Administration of Ren reduced the amount of Ruminococcus sp., Clostridiales bacteria, and Bacteroides dorei, and increased the amount of Prevotella. Real-time PCR results were consistent with the results derived by t-value biplots. These findings suggested that Ren is a potential agent for colon cancer prevention. In conclusion, the results in the present study suggest a potential therapeutic approach based on the modulation of intestinal microflora by probiotics may be beneficial in the prevention of colorectal carcinogenesis.

  4. Bifidobacterium breve MCC-117 Induces Tolerance in Porcine Intestinal Epithelial Cells: Study of the Mechanisms Involved in the Immunoregulatory Effect

    Science.gov (United States)

    MURATA, Kozue; TOMOSADA, Yohsuke; VILLENA, Julio; CHIBA, Eriko; SHIMAZU, Tomoyuki; ASO, Hisashi; IWABUCHI, Noriyuki; XIAO, Jin-zhong; SAITO, Tadao; KITAZAWA, Haruki

    2014-01-01

    Bifidobacterium breve MCC-117 is able to significantly reduce the expression of inflammatory cytokines in porcine intestinal epithelial (PIE) cells and to improve IL-10 levels in CD4+CD25high Foxp3+ lymphocytes in response to heat-stable enterotoxigenic Escherichia coli (ETEC) pathogen-associated molecular patterns (PAMPs), while the immunoregulatory effect of B. adolescentis ATCC15705 was significantly lower than that observed for the MCC-117 strain. Considering the different capacities of the two bifidobacterium strains to activate toll-like receptor (TLR)-2 and their differential immunoregulatory activities in PIE and immune cells, we hypothesized that comparative studies with both strains could provide important information regarding the molecular mechanism(s) involved in the anti-inflammatory activity of bifidobacteria. In this work, we demonstrated that the anti-inflammatory effect of B. breve MCC-117 was achieved by a complex interaction of multiple negative regulators of TLRs as well as inhibition of multiple signaling pathways. We showed that B. breve MCC-117 reduced heat-stable ETEC PAMP-induced NF-κB, p38 MAPK and PI3 K activation and expression of pro-inflammatory cytokines in PIE cells. In addition, we demonstrated that B. breve MCC-117 may activate TLR2 synergistically and cooperatively with one or more other pattern recognition receptors (PRRs), and that interactions may result in a coordinated sum of signals that induce the upregulation of A20, Bcl-3, Tollip and SIGIRR. Upregulation of these negative regulators could have an important physiological impact on maintaining or reestablishing homeostatic TLR signals in PIE cells. Therefore, in the present study, we gained insight into the molecular mechanisms involved in the immunoregulatory effect of B. breve MCC-117. PMID:24936377

  5. Cytogenetic insights into DNA damage and repair of lesions induced by a monomethylated trivalent arsenical

    Science.gov (United States)

    Arsenic is a human carcinogen, and only recently have animal models been developed that are useful in investigating its carcinogenic mode ofaction (MOA). However, how arsenic induces cancer is still an open question. In a previous paper, we proposed a model detailing how arsenic ...

  6. Chemoprotective Effect of Taurine on Potassium Bromate-Induced DNA Damage, DNA-Protein Cross-Linking and Oxidative Stress in Rat Intestine

    Science.gov (United States)

    Ahmad, Mir Kaisar; Khan, Aijaz Ahmed; Ali, Shaikh Nisar; Mahmood, Riaz

    2015-01-01

    Potassium bromate (KBrO3) is widely used as a food additive and is a major water disinfection by-product. It induces multiple organ toxicity in humans and experimental animals and is a probable human carcinogen. The present study reports the protective effect of dietary antioxidant taurine on KBrO3-induced damage to the rat intestine. Animals were randomly divided into four groups: control, KBrO3 alone, taurine alone and taurine+ KBrO3. Administration of KBrO3 alone led to decrease in the activities of intestinal brush border membrane enzymes while those of antioxidant defence and carbohydrate metabolism were also severely altered. There was increase in DNA damage and DNA-protein cross-linking. Treatment with taurine, prior to administration of KBrO3, resulted in significant attenuation in all these parameters but the administration of taurine alone had no effect. Histological studies supported these biochemical results showing extensive intestinal damage in KBrO3-treated animals and greatly reduced tissue injury in the taurine+ KBrO3 group. These results show that taurine ameliorates bromate induced tissue toxicity and oxidative damage by improving the antioxidant defence, tissue integrity and energy metabolism. Taurine can, therefore, be potentially used as a therapeutic/protective agent against toxicity of KBrO3 and related compounds. PMID:25748174

  7. Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice

    Directory of Open Access Journals (Sweden)

    Kyung-Hwa Jung

    2017-02-01

    Full Text Available Atopic dermatitis (AD is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg, and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

  8. Bee Venom Phospholipase A2 Ameliorates House Dust Mite Extract Induced Atopic Dermatitis Like Skin Lesions in Mice.

    Science.gov (United States)

    Jung, Kyung-Hwa; Baek, Hyunjung; Kang, Manho; Kim, Namsik; Lee, Seung Young; Bae, Hyunsu

    2017-02-18

    Atopic dermatitis (AD) is a biphasic inflammatory skin disease that is provoked by epidermal barrier defects, immune dysregulation, and increased skin infections. Previously, we have demonstrated that bvPLA2 evoked immune tolerance by inducing regulatory T cells (Treg), and thus alleviated Th2 dominant allergic asthma in mice. Here, we would like to determine whether treatment with bvPLA2 exacerbates the AD-like allergic inflammations induced by house dust mite extract (DFE) in a murine model. Epidermal thickness, immune cell infiltration, serum immunoglobulin, and cytokines were measured. Ear swelling, skin lesions, and the levels of total serum IgE and Th1/Th2 cytokines were elevated in DFE/DNCB-induced AD mice. Topical application of bvPLA2 elicited significant suppression of the increased AD symptoms, including ear thickness, serum IgE concentration, inflammatory cytokines, and histological changes. Furthermore, bvPLA2 treatment inhibited mast cell infiltration into the ear. On the other hand, Treg cell depletion abolished the anti-atopic effects of bvPLA2, suggesting that the effects of bvPLA2 depend on the existence of Tregs. Taken together, the results revealed that topical exposure to bvPLA2 aggravated atopic skin inflammation, suggesting that bvPLA2 might be a candidate for the treatment of AD.

  9. Analysis of damaged DNA / proteins interactions: Methodological optimizations and applications to DNA lesions induced by platinum anticancer drugs

    International Nuclear Information System (INIS)

    Bounaix Morand du Puch, Ch

    2010-10-01

    DNA lesions contribute to the alteration of DNA structure, thereby inhibiting essential cellular processes. Such alterations may be beneficial for chemotherapies, for example in the case of platinum anticancer agents. They generate bulky adducts that, if not repaired, ultimately cause apoptosis. A better understanding of the biological response to such molecules can be obtained through the study of proteins that directly interact with the damages. These proteins constitute the DNA lesions interactome. This thesis presents the development of tools aiming at increasing the list of platinum adduct-associated proteins. Firstly, we designed a ligand fishing system made of damaged plasmids immobilized onto magnetic beads. Three platinum drugs were selected for our study: cisplatin, oxali-platin and satra-platin. Following exposure of the trap to nuclear extracts from HeLa cancer cells and identification of retained proteins by proteomics, we obtained already known candidates (HMGB1, hUBF, FACT complex) but also 29 new members of the platinated-DNA interactome. Among them, we noted the presence of PNUTS, TOX4 and WDR82, which associate to form the recently-discovered PTW/PP complex. Their capture was then confirmed with a second model, namely breast cancer cell line MDA MB 231, and the biological consequences of such an interaction now need to be elucidated. Secondly, we adapted a SPRi bio-chip to the study of platinum-damaged DNA/proteins interactions. Affinity of HMGB1 and newly characterized TOX4 for adducts generated by our three platinum drugs could be validated thanks to the bio-chip. Finally, we used our tools, as well as analytical chemistry and biochemistry methods, to evaluate the role of DDB2 (a factor involved in the recognition of UV-induced lesions) in the repair of cisplatin adducts. Our experiments using MDA MB 231 cells differentially expressing DDB2 showed that this protein is not responsible for the repair of platinum damages. Instead, it appears to act

  10. Neuroprotective effect of Portulaca oleracea extracts against 6-hydroxydopamine-induced lesion of dopaminergic neurons

    Directory of Open Access Journals (Sweden)

    WALESKA B. MARTINS

    2016-01-01

    Full Text Available ABSTRACT The Portulaca oleracea L. (Portulacaceae is a cosmopolitan species with a wide range of biological activities, including antioxidant and neuroprotective actions. We investigated the effects of P. oleracea extracts in a 6-hydroxydopamine rat model of Parkinson's disease, a debilitating disorder without effective treatments. Chemical profiles of aqueous and ethanolic extracts of whole plant were analyzed by thin layer chromatography and the antioxidant activity was assessed by 2,2-diphenyl-1-picrilhidrazila method. Male Wistar rats received intrastriatal 6-hydroxydopamine and were treated with vehicle or extracts (oral, 200 and 400 mg/kg daily for two weeks. The behavioral open field test was conducted at days 1 and 15. Immunohistochemical analysis was performed 4 weeks after surgery to quantify tyrosine-hydroxylase cell counts in the substantia nigra pars compacta. Extracts presented antioxidant activity in concentrations above 300 µg/kg. The chromatographic analysis revealed the presence of Levodopa, alkaloids, flavonoids, saponins, tannins, terpenoids and polysaccharides. Both extracts improved motor recovery 15 days after lesion and protected from tyrosine-hydroxylase cell loss after 4 weeks, but these effects were more evident for the aqueous extract. Because the dopamine precursor is present, in addition to antioxidant compounds and neuroprotective effects, P. oleracea can be considered as potential strategy for treating Parkinson's disease.

  11. Neuroprotective effect of Portulaca oleracea extracts against 6-hydroxydopamine-induced lesion of dopaminergic neurons.

    Science.gov (United States)

    Martins, Waleska B; Rodrigues, Sheyla A; Silva, Hatamy K; Dantas, Camila G; Júnior, Waldecy DE Lucca; Filho, Lauro Xavier; Cardoso, Juliana C; Gomes, Margarete Z

    2016-09-01

    The Portulaca oleracea L. (Portulacaceae) is a cosmopolitan species with a wide range of biological activities, including antioxidant and neuroprotective actions. We investigated the effects of P. oleracea extracts in a 6-hydroxydopamine rat model of Parkinson's disease, a debilitating disorder without effective treatments. Chemical profiles of aqueous and ethanolic extracts of whole plant were analyzed by thin layer chromatography and the antioxidant activity was assessed by 2,2-diphenyl-1-picrilhidrazila method. Male Wistar rats received intrastriatal 6-hydroxydopamine and were treated with vehicle or extracts (oral, 200 and 400 mg/kg) daily for two weeks. The behavioral open field test was conducted at days 1 and 15. Immunohistochemical analysis was performed 4 weeks after surgery to quantify tyrosine-hydroxylase cell counts in the substantia nigra pars compacta. Extracts presented antioxidant activity in concentrations above 300 µg/kg. The chromatographic analysis revealed the presence of Levodopa, alkaloids, flavonoids, saponins, tannins, terpenoids and polysaccharides. Both extracts improved motor recovery 15 days after lesion and protected from tyrosine-hydroxylase cell loss after 4 weeks, but these effects were more evident for the aqueous extract. Because the dopamine precursor is present, in addition to antioxidant compounds and neuroprotective effects, P. oleracea can be considered as potential strategy for treating Parkinson's disease.

  12. Effect of bioglass on artificially induced enamel lesion around orthodontic brackets: OCT study

    Science.gov (United States)

    Bakhsh, Turki; Al-batati, Mohammed; Mukhtar, Mona; Al-Najjar, Mohammed; Bakhsh, Saud; Bakhsh, Abdulsalam; Bakry, Ahmad; Mandurah, Mona; Abbassy, Mona

    2018-02-01

    Background and Objective: White spot lesions (WSLs) are commonly seen after completing orthodontic treatment. Different approaches have been suggested to avoid such a complication. Recently, 45S5 bioglass (BG) was introduced as remineralizing agent. Therefore, the objective of this in-vitro study was to assess the effect of BG in remineralizing WSLs using Optical coherence tomography (OCT). Methods: Fifteen human premolar teeth were sectioned and bonded to orthodontic brackets with Transbond XT primer followed by Transbond PLUS color change adhesive (3M Unitek, USA) on their smooth surfaces according to the manufacturer's instructions. Then, all specimens were varnished excluding the area of interest (AOI) around the bonded restoration, immersed in demineralizing solution and imaged by cross-polarization OCT (CONT group), and the maximum pixel value (MPV) of the AOI were calculated. Then, they were subjected to remineralizing solutions and BG application followed by OCT imaging (REM group). Results: Mann-Whitney test showed the MPV of the AOI in REM was greatly increased and was significantly different from CONT (penamel by MPV technique. The BG has a great potential to remineralize enamel defects, however further investigation is required.

  13. ORAL LESIONS OF DRUG INDUCED ERYTHEMA MULTIFORME and ndash; REPORT OF THREE CASES

    Directory of Open Access Journals (Sweden)

    Shruthi Hegde

    2013-09-01

    Full Text Available Abstract: Erythema multiforme (EM is an acute, self-limited, and sometimes recurring skin condition considered to be a hypersensitivity reaction associated with certain infections and medications. A range of medications can trigger the EM. Non-steroidal anti-inflammatory drugs (NSAIDS which are most commonly prescribed for pain relief can also produce rare adverse reactions such as EM. EM is clinically characterized by a and lsquo; and lsquo;minor'' form and a and lsquo; and lsquo;major'' form. Only few reports have stated about oral EM as the third variant of EM. However it is unclear whether EM involving only oral mucosa is a separate entity or is a part of minor form of EM. In this report three cases of EM are discussed , in which two cases involved exclusively oral mucosal lesions and in one case skin manifestations along with oral mucosa was observed. Also the uncommon adverse effects of NSAIDS is highlighted in this report along with its management. [J Contemp Med 2013; 3(3.000: 193-196

  14. The Mechanism of Sevoflurane Preconditioning-Induced Protections against Small Intestinal Ischemia Reperfusion Injury Is Independent of Mast Cell in Rats

    Directory of Open Access Journals (Sweden)

    Xiaoliang Gan

    2013-01-01

    Full Text Available The study aimed to investigate whether sevoflurane preconditioning can protect against small intestinal ischemia reperfusion (IIR injury and to explore whether mast cell (MC is involved in the protections provided by sevoflurane preconditioning. Sprague-Dawley rats exposed to sevoflurane or treated with MC stabilizer cromolyn sodium (CS were subjected to 75-minute superior mesenteric artery occlusion followed by 2-hour reperfusion in the presence or absence of MC degranulator compound 48/80 (CP. Small intestinal ischemia reperfusion resulted in severe intestinal injury as demonstrated by significant elevations in intestinal injury scores and p47phox and gp91phox, ICAM-1 protein expressions and malondialdehyde and IL-6 contents, and MPO activities as well as significant reductions in SOD activities, accompanied with concomitant increases in mast cell degranulation evidenced by significant increases in MC counts, tryptase expression, and β-hexosaminidase concentrations, and those alterations were further upregulated in the presence of CP. Sevoflurane preconditioning dramatically attenuated the previous IIR-induced alterations except MC counts, tryptase, and β-hexosaminidase which were significantly reduced by CS treatment. Furthermore, CP exacerbated IIR injury was abrogated by CS but not by sevoflurane preconditioning. The data collectively indicate that sevoflurane preconditioning confers protections against IIR injury, and MC is not involved in the protective process.

  15. Comparison of the dose-response relationship of radiation-induced apoptosis in the hippocampal dentate gyrus and intestinal crypt of adult mice

    International Nuclear Information System (INIS)

    Kim, J. S.; Yang, M.; Kim, J.; Lee, D.; Kim, J. C.; Shin, T.; Kim, S. H.; Moon, C.

    2012-01-01

    The present study compared the dose-response curves for the frequency of apoptosis in mouse hippocampal dentate gyrus (DG) and intestinal crypt using whole-body gamma irradiation. The incidence of gamma-ray-induced apoptosis was measured using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end-labelling (TUNEL) method. TUNEL-positive apoptotic nuclei in the DG and intestinal crypt were increased in a dose-dependent pattern (0-2 Gy). The dose-response curves were linear-quadratic, with a significant relationship between the appearance of apoptosis and irradiation dose. The slopes of the dose-response curves in the DG were much steeper (∼5-6-fold) than those in the intestinal crypt within the range of 0-1 Gy exposure. Hippocampal DG might be a more effective and sensitive evaluation structure than the intestinal crypt to estimate the degree of radiation exposure in damaged organs of adult mice exposed to low irradiation dose. copy; The Author 2011. Published by Oxford Univ. Press. All rights reserved. (authors)

  16. Hepatoprotective Effects of Met-enkephalin on Acetaminophen-Induced Liver Lesions in Male CBA Mice

    OpenAIRE

    Martinić, Roko; Šošić, Hrvoje; Turčić, Petra; Konjevoda, Paško; Fučić, Aleksandra; Stojković, Ranko; Aralica, Gorana; Gabričević, Mario; Weitner, Tin; Štambuk, Nikola

    2014-01-01

    Recent histopathological investigations in patients with hepatitis suggested possible involvement of Met-enkephalin and its receptors in the pathophysiology of hepatitis. Consequently, we evaluated the potential hepatoprotective effects of this endogenous opioid pentapeptide in the experimental model of acetaminophen induced hepatotoxicity in male CBA mice. Met-enkephalin exhibited strong hepatoprotective effects in a dose of 7.5 mg/kg, which corresponds to the protective dose reported for se...

  17. Carboxymethyl chitin-glucan (CM-CG) protects human HepG2 and HeLa cells against oxidative DNA lesions and stimulates DNA repair of lesions induced by alkylating agents.

    Science.gov (United States)

    Slamenová, Darina; Kováciková, Ines; Horváthová, Eva; Wsólová, Ladislava; Navarová, Jana

    2010-10-01

    A large number of functional foods, including those that contain β-d-glucans, have been shown to prevent human DNA against genotoxic effects and associated development of cancer and other chronic diseases. In this paper, carboxymethyl chitin-glucan (CM-CG) isolated from Aspergillus niger was investigated from two standpoints: (1) DNA-protective effects against oxidative DNA damage induced by H(2)O(2) and alkylating DNA damage induced by MMS and MNNG, and (2) a potential effect on rejoining of MMS- and MNNG-induced single strand DNA breaks. The results obtained by the comet assay in human cells cultured in vitro showed that CM-CG reduced significantly the level of oxidative DNA lesions induced by H(2)O(2) but did not change the level of alkylating DNA lesions induced by MMS or MNNG. On the other side, the efficiency of DNA-rejoining of single strand DNA breaks induced by MMS and MNNG was significantly higher in HepG2 cells pre-treated with CM-CG. The antioxidative activity of carboxymethyl chitin-glucan was confirmed by the DPPH assay. Copyright © 2010 Elsevier Ltd. All rights reserved.

  18. Tiagabine treatment in kainic acid induced cerebellar lesion of dystonia rat model

    Science.gov (United States)

    Wang, Tsui-chin; Ngampramuan, Sukonthar; Kotchabhakdi, Naiphinich

    2016-01-01

    Dystonia is a neurological disorder characterized by excessive involuntary muscle contractions that lead to twisting movements. The exaggerated movements have been studied and have implicated basal ganglia as the point of origin. In more recent studies, the cerebellum has also been identified as the possible target of dystonia, in the search for alternative treatments. Tiagabine is a selective GABA transporter inhibitor, which blocks the reuptake and recycling of GABA. The study of GABAergic drugs as an alternative treatment for cerebellar induced dystonia has not been reported. In our study, tiagabine was i.p. injected into kainic acid induced, cerebellar dystonic adult rats, and the effects were compared with non-tiagabine injected and sham-operated groups. Beam walking apparatus, telemetric electromyography (EMG) recording, and histological verification were performed to confirm dystonic symptoms in the rats on post-surgery treatment. Involuntary dystonic spasm was observed with repetitive rigidity, and twisting movements in the rats were also confirmed by a high score on the dystonic scoring and a high amplitude on the EMG data. The rats with tiagabine treatment were scored based on motor amelioration assessed via beam walking. The result of this study suggests and confirms that low dose of kainic acid microinjection is sufficient to induce dystonia from the cerebellar vermis. In addition, from the results of the EMG recording and the behavioral assessment through beam walking, tiagabine is demonstrated as being effective in reducing dystonic spasm and may be a possible alternative therapeutic drug in the treatment of dystonia. PMID:28337103

  19. Radiation-induced emesis in the dog: effects of lesions and drugs

    International Nuclear Information System (INIS)

    Carpenter, D.O.; Briggs, D.B.; Knox, A.P.; Strominger, N.L.

    1986-01-01

    Dogs exposed to 8 Gy 60 Co gamma mid-abdominal irradiation exhibited emesis with an average latency of 102 min and an average of 7.4 episodes over 96 min. There were no significant changes in dogs subjected to a chronic bilateral subdiaphragmatic vagotomy, but emesis was prevented by ablation of the area postrema. Indomethacin pretreatment also prevented radiation-induced emesis in two of seven dogs and in the remainder reduced the average number of episodes. Domperidone pretreatment prevented radiation-induced emesis in all of four dogs tested. In electrophysiological studies recording from the area postrema the chemosensitive neurons were found to be normally silent in anesthetized preparations but excitable by a variety of emetic agents. After irradiation of the abdomen spontaneously active neurons were found with a discharge pattern that mirrored the behavioral pattern of postirradiation emesis. These studies are consistent with radiation-induced emesis being humorally mediated in the dog and implicate dopamine and/or prostaglandins as possible mediators

  20. Cat retinal ganglion cell receptive-field alterations after 6-hydroxydopamine induced dopaminergic amacrine cell lesions

    International Nuclear Information System (INIS)

    Maguire, G.W.; Smith, E.L. III

    1985-01-01

    Optic tract single-unit recordings were used to study ganglion cell response functions of the intact cat eye after 6-hydroxydopamine (6-OHDA) lesioning of the dopaminergic amacrine cell (AC) population of the inner retina. The impairment of the dopaminergic AC was verified by high pressure-liquid chromatography with electrochemical detection of endogenous dopamine content and by [ 3 H]dopamine high-affinity uptake; the dopaminergic ACs of the treated eyes demonstrated reduced endogenous dopamine content and reduced [ 3 H]dopamine uptake compared with that of their matched controls. Normal appearing [ 3 H]GABA and [ 3 H]-glycine uptake in the treated retinas suggests the absence of any nonspecific action of the 6-OHDA on the neural retina. The impairment of the dopaminergic AC population was found to alter a number of response properties in off-center ganglion cells, but this impairment had only a modest effect on the on-center cells. An abnormally high proportion of the off-center ganglion cells in the 6-OHDA treated eyes possessed nonlinear, Y-type receptive fields. These cells also possessed shift-responses of greater than normal amplitude, altered intensity-response functions, reduced maintained activities, and more transient center responses. Of the on-center type cells, only the Y-type on-center cells were affected by 6-OHDA, possessing higher than normal maintained activities and altered intensity-response functions. The on-center X-cells were unaffected by 6-OHDA treatment. The dopaminergic AC of the photopically adapted cat retina therefore modulates a number of ganglion cell response properties and within the limits of this study is most prominent in off-center ganglion cell circuitry

  1. Impact of diet-induced obesity on intestinal stem cells: hyperproliferation but impaired intrinsic function that requires insulin/IGF1.

    Science.gov (United States)

    Mah, Amanda T; Van Landeghem, Laurianne; Gavin, Hannah E; Magness, Scott T; Lund, P Kay

    2014-09-01

    Nutrient intake regulates intestinal epithelial mass and crypt proliferation. Recent findings in model organisms and rodents indicate nutrient restriction impacts intestinal stem cells (ISC). Little is known about the impact of diet-induced obesity (DIO), a model of excess nutrient intake on ISC. We used a Sox9-EGFP reporter mouse to test the hypothesis that an adaptive response to DIO or associated hyperinsulinemia involves expansion and hyperproliferation of ISC. The Sox9-EGFP reporter mouse allows study and isolation of ISC, progenitors, and differentiated lineages based on different Sox9-EGFP expression levels. Sox9-EGFP mice were fed a high-fat diet for 20 weeks to induce DIO and compared with littermates fed low-fat rodent chow. Histology, fluorescence activated cell sorting, and mRNA analyses measured impact of DIO on jejunal crypt-villus morphometry, numbers, and proliferation of different Sox9-EGFP cell populations and gene expression. An in vitro culture assay directly assessed functional capacity of isolated ISC. DIO mice exhibited significant increases in body weight, plasma glucose, insulin, and insulin-like growth factor 1 (IGF1) levels and intestinal Igf1 mRNA. DIO mice had increased villus height and crypt density but decreased intestinal length and decreased numbers of Paneth and goblet cells. In vivo, DIO resulted in a selective expansion of Sox9-EGFP(Low) ISC and percentage of ISC in S-phase. ISC expansion significantly correlated with plasma insulin levels. In vitro, isolated ISC from DIO mice formed fewer enteroids in standard 3D Matrigel culture compared to controls, indicating impaired ISC function. This decreased enteroid formation in isolated ISC from DIO mice was rescued by exogenous insulin, IGF1, or both. We conclude that DIO induces specific increases in ISC and ISC hyperproliferation in vivo. However, isolated ISC from DIO mice have impaired intrinsic survival and growth in vitro that can be rescued by exogenous insulin or IGF1.

  2. A single-strand specific lesion drives MMS-induced hyper-mutability at a double-strand break in yeast.

    Science.gov (United States)

    Yang, Yong; Gordenin, Dmitry A; Resnick, Michael A

    2010-08-05

    Localized hyper-mutability (LHM) can be important in evolution, immunity, and genetic diseases. We previously reported that single-strand DNA (ssDNA) can be an important source of damage-induced LHM in yeast. Here, we establish that the generation of LHM by methyl methanesulfonate (MMS) during repair of a chromosomal double-strand break (DSB) can result in over 0.2 mutations/kb, which is approximately 20,000-fold higher than the MMS-induced mutation density without a DSB. The MMS-induced mutations associated with DSB repair were primarily due to substitutions via translesion DNA synthesis at damaged cytosines, even though there are nearly 10 times more MMS-induced lesions at other bases. Based on this mutation bias, the promutagenic lesion dominating LHM is likely 3-methylcytosine, which is single-strand specific. Thus, the dramatic increase in mutagenesis at a DSB is concluded to result primarily from the generation of non-repairable lesions in ssDNA associated with DSB repair along with efficient induction of highly mutagenic ssDNA-specific lesions. These findings with MMS-induced LHM have broad biological implications for unrepaired damage generated in ssDNA and possibly ssRNA. Published by Elsevier B.V.

  3. Different effects of short- and long-chained fructans on large intestinal physiology and carcinogen-induced aberrant crypt foci in rats

    DEFF Research Database (Denmark)

    Poulsen, Morten; Molck, Anne-Marie; Jacobsen, Bodil Lund

    2002-01-01

    Inulin-type fructans, which are nondigestible carbohydrates, have been shown to modulate the number of induced preneoplastic lesions in the colon as well as the colonic microflora in laboratory animals. The present study was designed to investigate the effect of a short- and long-chained inulin...

  4. Intestinal Surgery.

    Science.gov (United States)

    Desrochers, André; Anderson, David E

    2016-11-01

    A wide variety of disorders affecting the intestinal tract in cattle may require surgery. Among those disorders the more common are: intestinal volvulus, jejunal hemorrhage syndrome and more recently the duodenal sigmoid flexure volvulus. Although general principles of intestinal surgery can be applied, cattle has anatomical and behavior particularities that must be known before invading the abdomen. This article focuses on surgical techniques used to optimize outcomes and discusses specific disorders of small intestine. Diagnoses and surgical techniques presented can be applied in field conditions. Copyright © 2016 Elsevier Inc. All rights reserved.

  5. Effects of size of Trichostrongylus colubriformis infections on histopathology of the mucosa along the whole small intestine in rabbits.

    Science.gov (United States)

    Hoste, H; Mallet, S

    1990-11-01

    The influence of population size of Trichostrongylus colubriformis on the structures of the small intestine, especially with regard to the development and origin of an intestinal adaptive response, was examined in experimentally infected rabbits. The effects of low (500 L3) and high (50,000 L3) infection on histological (villous length, mucosa to serosa ratio, crypt surface) and biochemical (protein content, alkaline phosphatase and leucine aminopeptidase activities) aspects of the mucosa were assessed along the whole small intestine. The presence of a small number of worms induced only minor mucosal changes, indicating a regenerative response of the intestinal epithelium. The role of a local small population of T. colubriformis in the development of a previously described adaptive response appeared thus to be limited. On the other hand, the 50,000 L3 inoculum was associated with severe lesions of villi, marked crypt hyperplasia and with a major reduction of enzyme activities. The changes were found along the whole length of the small intestine. These results suggest that the generally recognized dose-dependent pathogenicity of the intestinal nematode infections could be ascribed to two different processes: firstly, a greater severity of the lesions; secondly, more extensive damage leading to the disappearance of any adaptive intestinal region.

  6. Extracts of human atherosclerotic lesions modify LDL inducing enhanced macrophage uptake

    International Nuclear Information System (INIS)

    Hoff, H.F.; O'Neill, J.

    1986-01-01

    Both an LDL-like fraction isolated from human aortic plaques and LDL incubated with cultured aortic endothelial or smooth muscle cells have been shown to be internalized by macrophages in vitro in an unregulated fashion leading to foam cell formation. Lipid peroxidation induced by free radicals released from cells was shown to be responsible for cell-modified LDL. The authors incubated LDL with a supernatant fraction of leached, i.e. non-homogenized, extracts of aortic plaques for one hour at 37 0 C, to determine whether extracellular components present in arteries were also capable of modifying LDL. Extract-treated LDL showed the following changes relative to untreated LDL: 1) increased electrophretic mobility, 2) altered pattern of B-100 on SDS-PAGE, i.e. presence of a doublet with higher M/sub r/ than B-100, and 3) enhanced uptake by cultured mouse peritoneal macrophages as measured by increased degradation of 125 I-LDL, and increased stimulation of cholesterol esterification using 14 C-oleate. Extracts from homogenized plaques and grossly normal intima induced similar changes. The modification was tissue specific in that extracts of arteries but not of liver, muscle or skin modified LDL. Protease degradation of LDL during incubation was probably not responsible since inhibitors did not prevent modification. It is possible that products of lipid peroxidation present in extracellular lipid of arteries may propagate free radicals or be incorporated into LDL, leading to modifications similar to those found in cell-modified LDL

  7. Changes in the composition of intestinal fungi and their role in mice with dextran sulfate sodium-induced colitis.

    Science.gov (United States)

    Qiu, Xinyun; Zhang, Feng; Yang, Xi; Wu, Na; Jiang, Weiwei; Li, Xia; Li, Xiaoxue; Liu, Yulan

    2015-05-27

    Intestinal fungi are increasingly believed to greatly influence gut health. However, the effects of fungi on intestinal inflammation and on gut bacterial constitution are not clear. Here, based on pyrosequencing method, we reveal tha